User:Box73/sandbox

From Wikipedia, the free encyclopedia

The restaurant was closed by January 2000.[1][2][3][4][5][6][7]

[8]

[9]

Original Bob's Big Boy Restaurants
Unit
No.
Address City Condition Ref.
1 900 E Colorado Glendale demolished [10]
2 624 S San Fernando Road Burbank demolished [11]
3 3212 La Crescenta Ave. Glendale transformed [12]
4 115 W Broadway (original)
121 E Broadway (moved)
Glendale transformed [13]
5 1801 Colorado Eagle Rock transformed [14]
6 4211 W Riverside Dr Burbank in operation [15]
7 5353 Van Nuys Blvd Van Nuys demolished
8 1616 E Colorado Blvd Pasadena demolished [16]
9 3130 East Colorado Pasadena demolished [17]

3212 La Crescenta Ave, Glendale, CA 91208

Schenley Tunnel working refs[edit]

Ready for work: The last rail placed on the Junction Railroad[18]

Wanted — 20 brickmasons[19]

Work on the Junction Tunnel[20]

Capital and labor notes[21]

Death takes noted capitalist[22]

The great short cut: Finishing touches to the Junction Road[23]

Jaunt on the Junction: The connecting link of two great roads informally opened[24]

The Marginal Scheme: Full text of the new bill[25]

The Marginal Road: An afternoon spent at making ammendments[26]

Local lawmakers: The Union Railway ordinance passed finally[27]

Some prospect of fun: A lively contest likely to-day in select council: Over the Junction Railroad Bill—An indignation meeting—The Mayor's veto in full[28]

The Marginal Scheme: How the projectors were fooled on Thursday: Indignation among the Baltimore, Pittsburgh and Chicago railroad people[29]

Rebuked: The Marginal Scheme gets a black eye in select council: The ordinance rejected on first reading: But one vote needed for the utter defeat of the scheme[30]

Still searching: Fourth session of the councilmanix investigating committee: Peter McGee testifies to offers of marginal stoc and money but declines to name the briber[31]


"May we serve you, too? [Advertisement]". The Cincinnati Enquirer. July 30, 1970. p. 48. Retrieved December 10, 2017 – via Newspapers.com. {{cite news}}: Cite has empty unknown parameter: |dead-url= (help)[32]

frisch's[33]

copyedit of Frisch's early history[edit]

In 1905, Samuel Frisch opened the Frisch Cafe in Cincinnati, Ohio. Five years later he closed the café and moved to the Norwood suburb of Cincinnati eventually opening another small café there. In 1915 he built and opened Frisch's Stag Lunch. By the early 1920s, the successful restaurant moved to a larger structure and his sons, David, Reuben and Irving joined the business. When Sameul Frisch died in 1923, twenty year-old David assumed the leadership role.

In 1932 Dave Frisch sold his interest in Stag Lunch and opened his own Frisch's Café in Norwood. The café was a success, and in 1938 Frisch opened a second location. —the effects of the Great Depression led to bankruptcy and both units closed in 1938. A local businessman, Fred Cornuelle, counselled Frisch and a new restaurant and in 1939 the Mainliner opened on Wooster Pike in Fairfax. Cincinnati's first year-round drive-in, it was named after a passenger airplane flying overhead into nearby Lunken Airport. By 1944 a second Frisch's restaurant opened, designed to resemble George Washington's Mount Vernon home.[34]

Current Franchising Costs[edit]

Big Boy Restaurants International and Frisch's Big Boy Restaurants both continue to franchises in their exclusive territories, both using 20 year terms. As of 2014 Big Boy Restaurants International charges a $40,000 franchise fee, and an ongoing 4% royalty and up to 3% advertising fees based on weekly gross revenue.[35][36] (In most of Michigan the franchisee pays a 2% advertising fee and must spend an additional 1% on local advertising. Franchisees in the upper peninsula of Michigan or outside of Michigan pays a 0.5% advertising fee and must spend 1.5% on local advertising.)[37] As of 2015 Frisch's Big Boy charges a $30,000 franchise fee[38], and an ongoing 3.75% royalty and 2.5% advertising fees.[39] The majority of Big Boy Restaurant International units are franchised while the majority of Frisch's units are currently company owned.[40] Big Boy Restaurants International franchise agreements are not renewable but new agreements are required.[35]

In most of Michigan the franchisee pays a 2% advertising fee and must spend an additional 1% on local advertising. Franchisees in the upper peninsula of Michigan or outside of Michigan pays a 0.5% advertising fee and must spend 1.5% on local advertising.

  • Schoenbaum Hall (Ohio State)[41][42]
  • [43][44]
  • Schoenbaum Library (University of Charleston)[45]
  • Schoenbaum Family Enrichment Center (Charleston, WV)

a[46] b[47] c[48] d e f[49][50][51]

Chewing betel quid—a mixture of a mixture of betel nut (nuts from the Areca catechu palm) with calcium hydoxide, and betel (leaves from the Piper betle vine)—produces stimulant effects and euphoria. Several psychoactive substances may contribute to the euphoriant effect: arecoline (a parasympathetic stimulant), arecaidine and guvacine (GABA uptake inhibitors), from the betel nuts, and aromatic phenolic compounds from betel leaves (causing adrenal epinephrine and norepinephrine release).[52][53][54]

betel pepper leaves and areca nut with calcium hydoxide—produces stimulant effects and euphoria. The suspected euphoriants are arecoline (a parasympathetic stimulant), arecaidine and guvacine (GABA uptake inhibitors), and aromatic phenolic compounds from betel leaves (causing catecholamine release).[52]

--------------------------------------------------

Areca Nut[edit]

Chewing areca nut (seeds from the Areca catechu palm) with slaked lime (calcium hydroxide) produces stimulant effects and euphoria.[55][54][56] The major psychoactive ingredients – arecoline (a muscarinic receptor partial agonist)[54][57] and arecaidine (a GABA reuptake inhibitor)[58][59] – are responsible for the euphoric effect.[60][61]

--------------------------------------------------

Arecaidine (a GABA uptake inhibitor and receptor antagonist) is a stimulant and mild euphoriant.

muscarinic parasympathetic stimulant

Euphoria has also been noted to occur in a very small percentage of individuals who used pregabalin in controlled trials as a treatment for neuropathic pain associated with diabetic peripheral neuropathy.

[62] [53]


Pregabalin[edit]

Notes: The drug monograph reports euphoria for neuropathic pain but also fibromyalgia, and other studies do for other (or no) conditions, so neuropathic pain isn't necessary to mention. Controlled studies seem superfluous to mention.


Pregabalin induces dose dependent euphoria.[63][64] Occuring in a small percentage of individuals at recommended doses, euphoria is increasingly frequent at supratherapeutic doses (or with insufflation or intravenuous administration).[65][64][63] At doses five times the maximum recommended, intense euphoria is reported.[63]


ponent processes. Individual differences in the NAc's responses to monetary reward expectation explained the variance of pain modulation by way of placebo-induced analgesia. Rewards that are olfactory, gustatory, auditory, visual, and sexual produced an analgesic effect that involves the ventral striatum. However, paiory in outlining interfacing sensory and emotional pain components so that pain may be directly learned as a rewarding stimulus. For instance, pain of physical punishment may be the only sign of attention. Some pain may be an integral component of many pleasurable activities, be it sexual intercourse or consumption of a sizzling and spicy food. Conditioned cue-induced effects can also evoke pain symptomatology through backward n usually eclipses its opponent effect, namely, euphoria that only becomes noticeable with the conclusion of the proponent painful condition.

https://en.wikipedia.org/wiki/User:Box73/sandbox2

The pain-pleasure continuum is a key theconditioning. That is, euphoria of pain termination, particularly when combined with euphoria produced by an opioid analgesic, constitutes an intense teaching signal reinforcing more pain and pain behavior. Conversely, after repeated pairing, pain-related stress and negative affective states can grow into a conditioned stimulus eliciting future painful episodes.--[66]

test cite[67][66]

[68]

3,4-methylenedioxy-N-methylamphetamine[69]

asdf Opioids are substances that act on opioid receptors to produce morphine-like effects.[70] Opioids include opiates, an older term that refers to such drugs derived from opium, including morphine itself.[71] Other opioids are semi-synthetic and synthetic drugs such as hydrocodone, oxycodone and fentanyl; antagonist drugs such as naloxone and endogenous peptides such as the endorphins.[72] Opioid drugs are predominantly central nervous system agents, most often used medically to relieve pain.[73]

The side effects of opioids may include pruritus, sedation, nausea, respiratory depression, constipation, and euphoria. Tolerance and dependence will develop with continuous use, requiring increasing doses and leading to a withdrawal syndrome with abrupt discontinuation. The profound euphoria attracts recreational use; frequent and escalating recreational use of opioids typically results in addiction. Accidental overdose or concurrent use with other depressant drugs commonly results in death from respiratory depression. Because of opioid drugs' reputation for addiction and fatal overdose, most are highly controlled substances.

Primarily used for pain relief, including anesthesia, opioids are also approved to suppress cough, suppress diarrhea, treat addiction, reverse opioid overdose, and suppress opioid induced constipation,.[74] Extremely potent opioids are used to immobilize large mammals.[75] Opioids act by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract. These receptors mediate both the psychoactive and the somatic effects of opioids. Opioid drugs include partial agonists and antagonists, which produce moderate or no effect (respectively) but displace other opioids from binding in those receptors.

Opioids are among the world's oldest known drugs. The medical use of the opium poppy predates recorded history; recreational and religious use likewise precedes the common era. In the 19th century morphine was isolated and marketed, and the hypodermic needle invented, introducing rapid, metered administration of the primary active compound. Synthetic opioids were invented, and biological mechanisms discovered in the 20th century. Illicit production, smuggling, and addiction to opioids, prompted treaties, laws and policing which have realized limited success. In 2013 between 28 and 38 million people used opioids recreationally (0.6% to 0.8% of the global population between the ages of 15 and 65).[76] In 2011 an estimated 4 million people the United States used opioids recreationally or were dependent on them.[77] Current recreational use and addiction are attributed to over-prescription of opioid medications and inexpensive illicit heroin.[78][79][80] Conversely, fears about over-prescribing, exaggerated side effects and addiction from opioids are similarly blamed for under-treatment of pain.[81][82]

The terms opiate and narcotic are sometimes encountered as synonyms for opioid. Opiate is properly limited to the natural alkaloids found in the resin of the Papaver somniferum (opium poppy) although some authorities include semi-synthetic derivatives.[83][71] Narcotic, derived from numbness or sleep, is now a legal term that refers to cocaine and opioids, and their source materials; it is also loosely applied to any illegal or controlled psychoactive drug.[84][85] The term has pejorative connotations and its use is generally discouraged.[86][87]

  1. ^ B, Krista (March 1, 2021). "Big Boy's Burgers and Shakes / Reviews". Restaurant Guru. Archived from the original on July 19, 2021. Retrieved July 19, 2021. Closed permanently! 1/29/20
  2. ^ Zhang, Chenyang; Jin, Huaqing; Wen, Yi Feng; Yin, Guosheng (2021-09-28). "Efficacy of COVID-19 Treatments: A Bayesian Network Meta-Analysis of Randomized Controlled Trials". Frontiers in Public Health. 9: 729559. doi:10.3389/fpubh.2021.729559. ISSN 2296-2565. PMC 8506153. PMID 34650951.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  3. ^ Deng, J; Zhou, F; Ali, S; Heybati, K; Hou, W; Huang, E; Wong, C Y (2021-09-27). "Efficacy and safety of ivermectin for the treatment of COVID-19: a systematic review and meta-analysis". QJM: An International Journal of Medicine: hcab247. doi:10.1093/qjmed/hcab247. ISSN 1460-2725. PMC 8500108. PMID 34570241.
  4. ^ O Murchu, Eamon; Spillane, Susan; Byrne, Paula; O'Neill, Michelle; Harrington, Patricia; Ryan, Máirín (2021-06-22). "Interventions in an Ambulatory Setting to Prevent Progression to Severe Disease in Patients With COVID-19: A Systematic Review". The Annals of Pharmacotherapy: 10600280211028242. doi:10.1177/10600280211028242. ISSN 1542-6270. PMID 34157890.
  5. ^ Quincho-Lopez, Alvaro; Benites-Ibarra, Christeam A.; Hilario-Gomez, Maryori M.; Quijano-Escate, Renatta; Taype-Rondan, Alvaro (2021-11-02). "Self-medication practices to prevent or manage COVID-19: A systematic review". PLoS ONE. 16 (11): e0259317. doi:10.1371/journal.pone.0259317. ISSN 1932-6203. PMC 8562851. PMID 34727126.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  6. ^ Cheng, Qinglin; Chen, Junfang; Jia, Qingjun; Fang, Zijian; Zhao, Gang (2021-09-16). "Efficacy and safety of current medications for treating severe and non-severe COVID-19 patients: an updated network meta-analysis of randomized placebo-controlled trials". Aging (Albany NY). 13 (18): 21866–21902. doi:10.18632/aging.203522. ISSN 1945-4589. PMC 8507270. PMID 34531332.
  7. ^ Cruciani, Mario; Pati, Ilaria; Masiello, Francesca; Malena, Marina; Pupella, Simonetta; De Angelis, Vincenzo (2021-09-08). "Ivermectin for Prophylaxis and Treatment of COVID-19: A Systematic Review and Meta-Analysis". Diagnostics (Basel, Switzerland). 11 (9): 1645. doi:10.3390/diagnostics11091645. ISSN 2075-4418. PMC 8470309. PMID 34573986.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  8. ^ "Big Boy's Burgers and Shakes - Recent Reviews". xestaurantji. Archived from the original on July 19, 2021. Retrieved July 19, 2021.
  9. ^ gorden654. "Big Boy's Burgers and Shakes". Tripadvisor. Archived from the original on July 19, 2021. Retrieved July 19, 2021. Just returned home with our take-out order.... Date of visit: August 2019{{cite web}}: CS1 maint: numeric names: authors list (link)
  10. ^ Bob's Big Boy. "1950's, Bob's Big Boy No. 1 (Mid-Century Drive-in), 900 E Colorado Glendale, CA 91205". Pinterest. Retrieved July 9, 2021.{{cite web}}: CS1 maint: url-status (link)
  11. ^ Bob's Big Boy. "1970's, Bob's Big Boy No. 2, 624 S San Fernando Road, Burbank, CA 91502". Pinterest. Retrieved July 9, 2021.{{cite web}}: CS1 maint: url-status (link)
  12. ^ Bob's Big Boy. "1960's, Bob's Big Boy No. 3, 3212 La Crescenta Ave, Glendale, CA 91208". Pinterest. Retrieved July 9, 2021.{{cite web}}: CS1 maint: url-status (link)
  13. ^ Bob's Big Boy. "1940's, Bob's Big Boy No. 4, 121 E Broadway, Glendale, CA 91205". Pinterest. Retrieved July 9, 2021.{{cite web}}: CS1 maint: url-status (link)
  14. ^ Bob's Big Boy. "1959, Bob's Big Boy No. 5, 1801 Colorado, Eagle Rock, CA 90041". Pinterest. Retrieved July 9, 2021.{{cite web}}: CS1 maint: url-status (link)
  15. ^ Bob's Big Boy. "1950's, Bob's Big Boy No. 6, 4211 W Riverside Dr, Burbank, CA 91505". Pinterest. Retrieved July 9, 2021.{{cite web}}: CS1 maint: url-status (link)
  16. ^ Bob's Big Boy. "1950's, Bob's Big Boy No. 8, 1616 E Colorado Blvd, Pasadena, CA 91106". Pinterest. Retrieved July 9, 2021.{{cite web}}: CS1 maint: url-status (link)
  17. ^ Bob's Big Boy. "1950's, Bob's Big Boy No. 9, 3130 East Colorado, Pasadena, CA 91107". Pinterest. Retrieved July 9, 2021.{{cite web}}: CS1 maint: url-status (link)
  18. ^ "Ready for work: The last rail placed on the Junction Railroad". Pittsburgh Commercial Gazette. September 25, 1884. p. 2. Retrieved February 25, 2018 – via Newspapers.com. {{cite news}}: Cite has empty unknown parameter: |dead-url= (help); Unknown parameter |subscription= ignored (|url-access= suggested) (help) Free access icon
  19. ^ "Wanted — 20 brickmasons". Pittsburgh Commercial Gazette. May 19, 1884. p. 3. Retrieved February 25, 2018 – via Newspapers.com. {{cite news}}: Cite has empty unknown parameter: |dead-url= (help); Unknown parameter |subscription= ignored (|url-access= suggested) (help) Free access icon
  20. ^ "Work on the Junction Tunnel". Pittsburgh Commercial Gazette. August 8, 1883. p. 2. Retrieved February 25, 2018 – via Newspapers.com. {{cite news}}: Cite has empty unknown parameter: |dead-url= (help); Unknown parameter |subscription= ignored (|url-access= suggested) (help) Free access icon
  21. ^ "Capital and labor notes". Pittsburgh Commercial Gazette. May 19, 1883. p. 2. Retrieved February 25, 2018 – via Newspapers.com. {{cite news}}: Cite has empty unknown parameter: |dead-url= (help); Unknown parameter |subscription= ignored (|url-access= suggested) (help) Free access icon
  22. ^ "Death takes noted capitalist". Pittsburgh Gazette Times. December 6, 1906. p. 2. Retrieved February 25, 2018 – via Newspapers.com. {{cite news}}: Cite has empty unknown parameter: |dead-url= (help) Free access icon
  23. ^ "The great short cut: Finishing touches to the Junction Road". The Evening Penny Press. Pittsburgh. December 11, 1884. p. 1. Retrieved February 25, 2018 – via Newspapers.com. {{cite news}}: Cite has empty unknown parameter: |dead-url= (help) Free access icon
  24. ^ "Jaunt on the Junction: The connecting link of two great roads informally opened". Pittsburgh Daily Post. October 1, 1884. p. 4. Retrieved February 25, 2018 – via Newspapers.com. {{cite news}}: Cite has empty unknown parameter: |dead-url= (help) Free access icon
  25. ^ "The marginal scheme: Full text of the new bill". Pittsburgh Commercial Gazette. March 14, 1881. p. 4. Retrieved February 26, 2018 – via Newspapers.com. {{cite news}}: Unknown parameter |subscription= ignored (|url-access= suggested) (help) Free access icon
  26. ^ "The marginal road: An afternoon spent at making ammendments". Pittsburgh Daily Post. January 5, 1881. p. 4. Retrieved February 26, 2018 – via Newspapers.com. {{cite news}}: Cite has empty unknown parameter: |dead-url= (help); Unknown parameter |subscription= ignored (|url-access= suggested) (help) Free access icon
  27. ^ "Local lawmakers: The Union Railway ordinance passed finally". Pittsburgh Commercial Gazette. June 29, 1881. p. 2. Retrieved February 26, 2018 – via Newspapers.com. {{cite news}}: Cite has empty unknown parameter: |dead-url= (help); Unknown parameter |subscription= ignored (|url-access= suggested) (help) Free access icon
  28. ^ "Some prospect of fun: A lively contest likely to-day in select council: Over the Junction Railroad Bill—An indignation meeting—The Mayor's veto in full". Pittsburgh Daily Post. July 30, 1883. p. 4. Retrieved February 26, 2018 – via Newspapers.com. {{cite news}}: Cite has empty unknown parameter: |dead-url= (help); Unknown parameter |subscription= ignored (|url-access= suggested) (help) Free access icon
  29. ^ "The Marginal Scheme: How the projectors were fooled on Thursday: Indignation among the Baltimore, Pittsburgh and Chicago railroad people". Pittsburgh Daily Post. January 22, 1881. p. 4. Retrieved February 26, 2018 – via Newspapers.com. {{cite news}}: Cite has empty unknown parameter: |dead-url= (help); Unknown parameter |subscription= ignored (|url-access= suggested) (help) Free access icon
  30. ^ "Rebuked: The Marginal Scheme gets a black eye in select council: The ordinance rejected on first reading: But one vote needed for the utter defeat of the scheme". Pittsburgh Daily Post. January 21, 1881. p. 4. Retrieved February 26, 2018 – via Newspapers.com. {{cite news}}: Cite has empty unknown parameter: |dead-url= (help); Unknown parameter |subscription= ignored (|url-access= suggested) (help) Free access icon
  31. ^ "Still searching: Fourth session of the councilmanix investigating committee: Peter McGee testifies to offers of marginal stock and money but declines to name the briber". Pittsburgh Daily Post. February 24, 1883. p. 4. Retrieved February 26, 2018 – via Newspapers.com. {{cite news}}: Cite has empty unknown parameter: |dead-url= (help); Unknown parameter |subscription= ignored (|url-access= suggested) (help) Free access icon
  32. ^ Slominski AT, Zmijewski MA, Skobowiat C, Zbytek B, Slominski RM, Steketee JD (January 2012). "Sensing the environment: regulation of local and global homeostasis by the skin's neuroendocrine system". Advances in Anatomy, Embryology, and Cell Biology. 212: v, vii, 1–115. ISSN 0301-5556. PMC 3422784. PMID 22894052. These concepts are underscored by the observation that humans and horses exposed to sunlight led to increased serum levels of α-MSH and ACTH (Holtzmann, 1982, Holtzmann, 1983), while experimental whole body exposure to UVB increased β-LPH and β-endorphin serum levels (Belon, 1985, Levins et al., 1983).... Lastly, our model may provide mechanistic explanation of the recently described phenomenon of 'UVR addiction' (Kourosh et al., 2010, Nolan et al., 2009) caused by cutaneous β-endorphin production.
  33. ^ "May we serve you, too? [Advertisement]". The Cincinnati Enquirer. July 30, 1970. p. 48. Retrieved December 10, 2017 – via Newspapers.com. {{cite news}}: Cite has empty unknown parameter: |dead-url= (help) Note: The Big Boy character copyright is dated 1969. Free access icon
  34. ^ "History of Frisch's Restaurants, Inc.". International Directory of Company Histories. Vol. 35. St. James Press. 2001. Retrieved April 17, 2014.
  35. ^ a b "Big Boy Restaurants Int'l. Franchise Information". Entrepreneur. Retrieved March 27, 2017. {{cite web}}: Cite has empty unknown parameter: |dead-url= (help)
  36. ^ "Bob's Big Boy FAQ's" (PDF). BigBoy.com. Retrieved March 27, 2017. {{cite web}}: |archive-date= requires |archive-url= (help); Check date values in: |archive-date= (help); Cite has empty unknown parameter: |dead-url= (help)
  37. ^ "Big Boy Franchise Management Franchise Agreement" (PDF). Franchise-Info,ca. 2012. pp. 8–9. Retrieved March 27, 2017. {{cite web}}: Cite has empty unknown parameter: |dead-url= (help)
  38. ^ "Frisch's Big Boy Franchise". www.franchisegrade.com. Retrieved March 28, 2017. {{cite web}}: Cite has empty unknown parameter: |dead-url= (help)
  39. ^ "Frisch's Big Boy Analyst Notes & Comparative Analysis". www.franchisegrade.com. Retrieved March 28, 2017. {{cite web}}: Cite has empty unknown parameter: |dead-url= (help)
  40. ^ "Frisch's At-A-Glance" (PDF). frischs.com. Retrieved March 27, 2017. {{cite web}}: Cite has empty unknown parameter: |dead-url= (help)
  41. ^ "Most of Schoenbaum Estate Goes to Sons". Charleston Gazette. August 5, 1951. p. 5. Retrieved October 1, 2016 – via newspaperarchive.com.
  42. ^ "Arm & Hammer Baking Soda – Basics – The Magic of Arm & Hammer Baking Soda". armandhammer.com. Archived from the original on 31 August 2009. Retrieved 30 July 2009. {{cite web}}: Unknown parameter |dead-url= ignored (|url-status= suggested) (help)
  43. ^ "Big Boy lookalike event to celebrate Founder's Day". Fox19 Now. Retrieved October 8, 2016. On Thursday, Frisch's Big Boy will be celebrating the birthday of its founder, David Frisch, by hosting a Big Boy lookalike event.
  44. ^ "Frisch's Founder's Day: Dress like Big Boy, get a Big Boy free!". Facebook. May 3, 2013. Retrieved October 8, 2016. May 3 marks the second annual Frisch's Founder's Day and we want to celebrate Dave Frisch's birthday with you!
  45. ^ Sonis, Larry (December 8, 2015). "Alex Schoenbaum". e-WV: The West Virginia Encyclopedia. West Virginia Humanities Council. Retrieved October 1, 2016.
  46. ^ "NRD Capital Management, LLC: Private Company Information". www.bloomberg.com. Bloomberg. Retrieved November 26, 2016.
  47. ^ "NRD Capital | Franchise Funding". www.nrdcapital.com. Retrieved November 26, 2016.
  48. ^ "Company Overview | National Restaurant Development". National Restaurant Development Holdings. Retrieved November 26, 2016.
  49. ^ "National Restaurant Development: About NRD". nrdiusa.com. Retrieved November 29, 2016.
  50. ^ "NRD Capital | Franchise Funding". www.nrdcapital.com. Retrieved November 29, 2016.
  51. ^ "NRD Capital Management". www.crunchbase.com. Retrieved November 29, 2016.
  52. ^ a b Norton SA (January 1998). "Betel: consumption and consequences" (PDF). Journal of the American Academy of Dermatology. 38 (1): 81–88. ISSN 0190-9622. PMID 9448210. Betel chewing has been claimed to produce a sense of well-being, euphoria, heightened alertness, sweating, salivation, a hot sensation in the body and increased capacity to work.
  53. ^ a b Chu NS (January 2002). "Neurological aspects of areca and betel chewing". Addiction Biology. 7 (1): 111–114. doi:10.1080/13556210120091473. ISSN 1355-6215. PMID 11900630. Betel quid chewing has been claimed to produce a sense of well-being, euphoria, warm sensation of the body, sweating, salivation, palpitation, heightened alertness and increased capacity to work. ... Although arecoline has been thought to be responsible for several effects of betel quid chewing, the present data suggest a role also played by sympathetic activation.
  54. ^ a b c Garg A, Chaturvedi P, Gupta PC (June 2014). "A review of the systemic adverse effects of areca nut or betel nut". Indian Journal of Medical and Paediatric Oncology. 35: 3, 4. It is one of the most widely consumed addictive substances in the world after nicotine, ethanol and caffeine, and is consumed by approximately 10% of the world's population.... The users of areca nut believe that it is helpful for the digestive system and has mild euphoric effects. ...
         The major parasympathetic and muscarinic effects of areca nut are due to arecoline.
  55. ^ Cox S, Ullah M, Zoellner H (2016). "Oral and Systemic Health Effects of Compulsive Areca Nut Use". In Preedy VR (ed.). Neuropathology of Drug Addictions and Substance Misuse Volume 3: General Processes and Mechanisms, Prescription Medications, Caffeine and Areca, Polydrug Misuse, Emerging Addictions and Non-Drug Addictions. Academic Press. p. 791. ISBN 9780128006771. The areca nut is the fourth most used drug after nicotine, alcohol, and caffeine. The effects are described as pleasurable and generally stimulating, inducing a sense of well-being, euphoria, heightened alertness, a warm sensation throughout the body, and an increased capacity to work.
  56. ^ Sharan RN, Mehrotra R, Choudhury Y, Asotra K (August 2012). "Association of Betel Nut with Carcinogenesis: Revisit with a Clinical Perspective". PLOS ONE. 7 (8): e42759. doi:10.1371/journal.pone.0042759. ISSN 1932-6203. PMC 3418282. PMID 22912735.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  57. ^ Riviere JE, Papich MG (2013). Veterinary Pharmacology and Therapeutics. John Wiley & Sons. p. 165. ISBN 9781118685907. Pilocarpine, arecoline and muscarine are rather selective parasympathetic agents; i.e., their cholinomimetic activity is exerted primarily at muscarinic sites with minimal nicotinic effects.
  58. ^ Liu YJ, Peng W, Hu MB, Xu M, Wu CJ (November 2016). "The pharmacology, toxicology and potential applications of arecoline: a review". Pharmaceutical Biology. 54 (11): 2753. doi:10.3109/13880209.2016.1160251. ISSN 1744-5116. PMID 27046150.
  59. ^ Peng W, Liu YJ, Wu N, Sun T, He XY, Gao YX, Wu CJ (April 2015). "Areca catechu L. (Arecaceae): a review of its traditional uses, botany, phytochemistry, pharmacology and toxicology". Journal of Ethnopharmacology. 164: 348. doi:10.1016/j.jep.2015.02.010. ISSN 1872-7573. PMID 25681543. Previous investigations indicated that the arecaidine and guvacine isolated from the A. catechu are effective antagonists of GABA, with IC50 values 122712 μM and 871 μM, respectively (Johnston et al., 1975; Lodge et al., 1977).{{cite journal}}: CS1 maint: multiple names: authors list (link)
  60. ^ Arif A, Westermeyer J (2012). Manual of Drug and Alcohol Abuse: Guidelines for Teaching in Medical and Health Institutions. New York: Springer Science & Business Media. pp. 159–160. ISBN 9781461595168.
  61. ^ Aronson, J. K. (2009). Meyler's Side Effects of Herbal Medicines. Elsevier. p. 53. ISBN 9780444532695. The lime in the betel quid causes hydrolysis of arecoline to arecailide, a central nervous stimulant, which accounts, together with the essential oil of the betel pepper, for the euphoric effects of chewing betel quid.
  62. ^ Fugmann B, Lang-Fugmann S, Steglich W (2014). RÖMPP Encyclopedia Natural Products, 1st Edition, 2000. Stuttgart, Germany: Georg Thieme Verlag. p. 164. ISBN 9783131795519.
  63. ^ a b c Martinotti G, Papazisis G, Santacroce R, Kouvelas D, Cinosi E, Lupi M, di Giannantonio M (2016). "Pregabalin Abuse and Addiction". In Preedy VR (ed.). Neuropathology of Drug Addictions and Substance Misuse Volume 3: General Processes and Mechanisms, Prescription Medications, Caffeine and Areca, Polydrug Misuse, Emerging Addictions and Non-Drug Addictions. London: Academic Press. pp. 948–949. ISBN 9780128006771. Exceeding the therapeutic doses, pregabalin is described as an 'ideal psychotropic drug' for recreational purposes, including alcohol/GHB/benzodiazepine-like effects, euphoria, entactogenic feelings, and dissociation. ...
         Up to 1200mg ... euphoria ... Over 1500mg ... intense euphoria
  64. ^ a b Schjerning O, Rosenzweig M, Pottegård A, Damkier P, Nielsen J (January 2016). "Abuse Potential of Pregabalin: A Systematic Review" (PDF). CNS drugs. 30 (1): 9. doi:10.1007/s40263-015-0303-6. ISSN 1179-1934. PMID 26767525. Pregabalin is, in some cases, used for recreational purposes and it has incurred attention among drug abusers for causing euphoric and dissociative effects when taken in doses exceeding normal therapeutic dosages or used by alternative routes of administration, such as nasal insufflation or venous injection.
  65. ^ "Lyrica". Drugs.com. Retrieved 20 August 2016.
  66. ^ a b Elman, Igor; Borsook, David (2016-01-06). "Common Brain Mechanisms of Chronic Pain and Addiction". Neuron. 89 (1): 11–36. doi:10.1016/j.neuron.2015.11.027. ISSN 1097-4199. PMID 26748087.
  67. ^ "FDA Approved Drug Products: Label and Approval History (Benzedrine)". www.accessdata.fda.gov. Retrieved 11 March 2016. Action Date 5/11/1982, Supplement Number 007, Approval Type Chemistry
  68. ^ Laycock, Thomas (4 January 1862). The Medical Times & Gazette. London: John Churchill. p. 1. Not unfrequently, indeed, the appearance of the patient is more diagnostic than his feelings. This is the case in some very grave diseases, in which that portion of the nervous system which subserves to the feeling of bodily well-being,—termed, in psychological phrase, euphoria—is morbidly modified as to function.
  69. ^ Skrinska, Victor A.; Gock, Susan B. (2005-01-01). "Measurement of 3,4-MDMA and related amines in diagnostic and forensic laboratories". Clinical Laboratory Science: Journal of the American Society for Medical Technology. 18 (2): 119–123. ISSN 0894-959X. PMID 15916245.
  70. ^ Hemmings, Hugh C.; Egan, Talmage D. (2013). Pharmacology and Physiology for Anesthesia: Foundations and Clinical Application: Expert Consult - Online and Print. Elsevier Health Sciences. p. 253. ISBN 1437716792. Opiate is the older term classically used in pharmacology to mean a drug derived from opium. Opioid, a more modern term, is used to designate all substances, both natural and synthetic, that bind to opioid receptors (including antagonists).
  71. ^ a b Offermanns, Stefan (2008). Encyclopedia of Molecular Pharmacology. Vol. 1 (2 ed.). Springer Science & Business Media. p. 903. ISBN 9783540389163. In the strict sense, opiates are drugs derived from opium and include the natural products morphine, codeine, thebaine and many semi-synthetic congeners derived from them. In the wider sense, opiates are morphine-like drugs with non peptidic structures. The older term opiates is now more and more replaced by the term opioids which applies to any substance, whether endogenous or synthetic, peptidic or non-peptidic, that produces morphine-like effects through action on opioid receptors.
  72. ^ Freye, Enno (2008). "Part II. Mechanism of action of opioids and clinical effects". Opioids in Medicine: A Comprehensive Review on the Mode of Action and the Use of Analgesics in Different Clinical Pain States. Springer Science & Business Media. p. 85. ISBN 9781402059476. Opiate is a specific term that is used to describe drugs (natural and semi-synthetic) derived from the juice of the opium poppy. For example morphine is an opiate but methadone (a completely synthetic drug) is not. Opioid is a general term that includes naturally occurring, semi-synthetic, and synthetic drugs, which produce their effects by combining with opioid receptors and are competively antagonized by nalaxone. In this context the term opioid refers to opioid agonists, opioid antagonist, opioid peptides, and opioid receptors.
  73. ^ Benzon, Honorio; Raja, Srinivasa N.; Fishman, Scott E.; Liu, Spencer; Cohen, Steven P. (2011). Essentials of Pain Medicine. Elsevier Health Sciences. p. 85. ISBN 1437735932.
  74. ^ Stromgaard, Kristian; Krogsgaard-Larsen, Povl; Madsen, Ulf (2009). Textbook of Drug Design and Discovery, Fourth Edition. CRC Press. ISBN 9781439882405.
  75. ^ Sterken, Joeri; Troubleyn, Joris; Gasthuys, Frank; Maes, Viviane; Diltoer, Mark; Verborgh, Christian (2004-10-01). "Intentional overdose of Large Animal Immobilon". European Journal of Emergency Medicine: Official Journal of the European Society for Emergency Medicine. 11 (5): 298–301. ISSN 0969-9546. PMID 15359207.
  76. ^ "Status and Trend Analysis of Illict [sic] Drug Markets". World Drug Report 2015 (PDF). Retrieved 26 June 2015.
  77. ^ "Report III: FDA Approved Medications for the Treatment of Opiate Dependence: Literature Reviews on Effectiveness & Cost- Effectiveness, Treatment Research Institute". Advancing Access to Addiction Medications: Implications for Opioid Addiction Treatment. p. 41.
  78. ^ Tetrault, Jeanette M.; Butner, Jenna L. (2015-09-03). "Non-Medical Prescription Opioid Use and Prescription Opioid Use Disorder: A Review". The Yale Journal of Biology and Medicine. 88 (3): 227–233. ISSN 0044-0086. PMC 4553642. PMID 26339205.
  79. ^ Tarabar, Asim F.; Nelson, Lewis S. (2003-04-01). "The resurgence and abuse of heroin by children in the United States". Current Opinion in Pediatrics. 15 (2): 210–215. ISSN 1040-8703. PMID 12640281.
  80. ^ Gray, Eliza (2014-02-04). "Heroin Gains Popularity as Cheap Doses Flood the U.S." TIME.com. Retrieved 2016-02-12.
  81. ^ Maltoni, M. (2008-01-01). "Opioids, pain, and fear". Annals of Oncology. 19 (1): 5–7. doi:10.1093/annonc/mdm555. ISSN 0923-7534. PMID 18073220. [A] number of studies, however, have also reported inadequate pain control in 40%–70% of patients, resulting in the emergence of a new type of epidemiology, that of 'failed pain control', caused by a series of obstacles preventing adequate cancer pain management.... The cancer patient runs the risk of becoming an innocent victim of a war waged against opioid abuse and addiction if the norms regarding the two kinds of use (therapeutic or nontherapeutic) are not clearly distinct. Furthermore, health professionals may be worried about regulatory scrutiny and may opt not to use opioid therapy for this reason.
  82. ^ McCarberg, Bill H. (2011-03-01). "Pain management in primary care: strategies to mitigate opioid misuse, abuse, and diversion". Postgraduate Medicine. 123 (2): 119–130. doi:10.3810/pgm.2011.03.2270. ISSN 1941-9260. PMID 21474900.
  83. ^ ARNP, Pamela Davies MS; CNS, Yvonne D'Arcy MS, CRNP (2012-09-26). Compact Clinical Guide to Cancer Pain Management: An Evidence-Based Approach for Nurses. Springer Publishing Company. ISBN 9780826109743.{{cite book}}: CS1 maint: multiple names: authors list (link)
  84. ^ "21 U.S. Code § 802 - Definitions". LII / Legal Information Institute. Retrieved 2016-02-12.
  85. ^ "Definition of NARCOTIC". www.merriam-webster.com. Retrieved 2016-02-12.
  86. ^ Satoskar, R. S.; Rege, Nirmala; Bhandarkar, S. D. (2015). Pharmacology and Pharmacotherapeutics. Elsevier Health Sciences. ISBN 9788131243718.
  87. ^ Ebert, Michael H.; Kerns, Robert D. (2010). Behavioral and Psychopharmacologic Pain Management. Cambridge University Press. ISBN 9781139493543.

Although the term opiate is often used as a synonym for opioid, the term {{opiate is properly limited to the natural alkaloids found in the resin of the Papaver somniferum (opium poppy), while opioid refers to both natural and synthetic compounds with an opium-like effect (by being agonists at the opioid receptor). i.e. all opiates are opioids, but not all opioids are opiates.[1] Semi-synthetic opioids such as heroin, hydrocodone and oxycodone are sometimes classified as opiates. Because morphine does not act on all types of opioid receptors and these receptors produce different effects, opioids are now primarily defined by binding to opioid receptors rather than by morphine-like effects.

Opioid drugs include antagonists, inactive opioids that prevent other opioids from binding, and partial agonists that produce a moderate effect while prevening other opioids from binding.

Opioids are substances that act on the nervous system in a similar way to opiates such as morphine and codeine.[2] In a medical context the term usually indicates medications that are artificially made rather than extracted from opium.[1] Common examples include oxycodone, hydrocodone, and hydromorphone.[3] Opioids are primarily used in medicine for the treatment of pain.

Opioids are substances that act on opioid receptors to produce morphine-like effects.[4] Opioids include opiates, an older term that refers to such drugs derived from opium, including morphine itself.[5] Other opioids are semi-synthetic and synthetic drugs such as hydrocodone, oxycodone and fentanyl; antagonist drugs such as naloxone and endogenous substances such as endorphins.[6] Opioid drugs are predominantly central nervous system agents, most often used medically to relieve pain.[7]

The side effects of opioids may include pruritus, sedation, respiratory depression, constipation, and euphoria. Tolerance and dependence will develop with continuous use, requiring increasing doses and leading to a withdrawal syndrome with abrupt discontinuation. The profound euphoria invites recreational use; continuous and escalating recreational use of opioids typically results in addiction. Accidental overdose or concurrent use with other depressant drugs commonly results in death from respiratory depression. Because of opioid drugs' reputation for addiction and fatal overdose, most are highly controlled substances.

Morphine-like opioids are well known for their addictive properties, and for their ability to produce euphoria, motivating some to use opioids recreationally.

A number of substances occurring naturally in the body that can decrease the sensation of pain are also classified as opioids. Opioid like compounds found in natural opium latex are classified as opiates, but are also opioids.

Primarily used for pain relief, opioids are also approved to provide anesthesia, suppress cough, suppress diarrhea, treat addiction and reverse opioid overdose.[8] Highly potent opioids are used to tranquilize large mammals. Most opioid drugs are controlled subtances. Opioids act by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract. These receptors mediate both the psychoactive and the somatic effects of opioids. Opioid drugs include antagonists, inactive opioids that prevent other opioids from binding, and partial agonists that produce a moderate effect while prevening other opioids from binding.

Opioids are among the world's oldest known drugs. The medical use of the opium poppy predates recorded history; recreational and religious use likewise precedes the common era. In the 19th century morphine was isolated and marketed, and the hypodermic needle invented.introducing rapid, controlled administration. Synthetic opioids were invented, and biological mechanisms discovered in the 20th century. Illicit production and addiction to opioids, prompted treaties, laws and police actions with limited success. In 2013 between 28 and 38 million people used opioids recreationally (0.6% to 0.8% of the global population between the ages of 15 and 65).[9] In 2011 about 4 million people the United States used opioids recreationally or were dependent on them.[10] Current recreational use and addiction are attributed to over prescription of opioid medications and falling prices for illicit heroin.

Although the term opiate is often used as a synonym for opioid, the term opiate is properly limited to the natural alkaloids found in the resin of the Papaver somniferum (opium poppy), while opioid refers to both natural and synthetic compounds with an opium-like effect (by being agonists at the opioid receptor). i.e. all opiates are opioids, but not all opioids are opiates.[1] Semi-synthetic opioids such as heroin, hydrocodone and oxycodone are sometimes classified as opiates.

Opioids are substances that act on opioid receptors to produce morphine-like effects. Opioids include opiates, an older term that refers to such drugs derived from opium, including morphine itself. Other opioids are semi-synthetic and synthetic drugs such as hydrocodone, oxycodone and fentanyl; antagonist drugs such as naloxone and endogenous susbtances such as endorphins. Opioid drugs are predominantly central nervous system agents, most often used medically to relieve pain.

The lead paragraph definition of opioid should be replaced. It does not reflect the predominant definition which includes all such substances, including opiates. The second sentence isn't true and the third is really just defining non-opiates. Codeine likewise is mentioned to reinforce this opiate distinction. Relegating the predominant modern definition isn't appropriate.

I propose the following lead paragraph:

Opioids are all drugs and endogenous substances that act on opioid receptors to produce morphine-like effects. It includes opiates, an older term that refers to such drugs derived from opium, including morphine itself. Opioid drugs are predominantly central nervous system agents, most often used medically to relieve pain.

1. Central could be cut to include peripheral actions but the article, literature and uses all deal overwhelmingly with CNS actions. 2. The first sentence could be expanded to "to produce or prevent morphine-like effects," to accommodate opioid antagonists which are technically opioids; 3. "drugs and endogenous substances" could be cut to "substances".

Because this lead issue has been so contentious, I cite the following:

Opiate is the older term classically used in pharmacology to mean a drug derived from opium. Opioid, a more modern term, is used to designate all substances, both natural and synthetic, that bind to opioid receptors (including antagonists). (p 253)

— Pharmacology and Physiology for Anesthesia: Foundations and Clinical Application [11]

In the strict sense, opiates are drugs derived from opium and include the natural products morphine, codeine, thebaine and many semi-synthetic congeners derived from them. In the wider sense, opiates are morphine-like drugs with non peptidic structures. The older term opiates is now more and more replaced by the term opioids which applies to any substance, whether endogenous or synthetic, peptidic or non-peptidic, that produces morphine-like effects through action on opioid receptors. (p 903)

Encyclopedia of Molecular Pharmacology [12]

Opiate is a specific term that is used to describe drugs (natural and semi-synthetic) derived from the juice of the opium poppy. For example morphine is an opiate but methadone (a completely synthetic drug) is not. Opioid is a general term that includes naturally occurring, semi-synthetic, and synthetic drugs, which produce their effects by combining with opioid receptors and are competively antagonized by nalaxone. In this context the term opioid refers to opioid agonists, opioid antagonist, opioid peptides, and opioid receptors. (p. 85)

— Opioids in Medicine: A Comprehensive Review on the Mode of Action
and the Use of Analgesics in Different Clinical Pain States
[13]

An opiate, strictly defined, is a drug extracted from the exudate of the poppy. Therefore the term is restricted to two drugs found in the exudates: morphine and codeine. An opioid is any exogenous drug (natural, semisynthetic, or synthetic) that binds to an opiate receptor and produces agonistic, or morphinelike, effects. (p. 322) [This quote from the 12th edition (2011) of the book is an evolution from the 5th edition (1988) where "opiate refers to any natural or synthetic drug that exerts actions on the body in a way similar to those induced by morphine...". (p. 121)]

— A Primer of Drug Action [14]

Opiates are drugs derived from opium, the extract of the seeds of the opium poppy, and include morphine, codeine, and heroin. The term opioid is more comprehensive and includes all agonists and antagonists with morphine-like activity, including natural opiates, semisynthetic drugs such as hydrocodone and hydromorphone, and synthetic drugs, such as oxycodone, methadone, buprenorphine, and fentanyl.

— The ASAM Essentials of Addiction Medicine [15]

In this paper, the term, "opioid," is used in the sense originally proposed by Dr. George H. Acheson (personal communication) to refer to any chemical compound with morphine-like properties.(footnote, p. 55)

— "Factors Regulating Oral Consumption of an Opioid (Etonitazene)
by Morphine-Addicted Rats" in Psychopharmacologia [16]

The term opioid refers to all compounds that bind to opiate receptors. Conventionally, the term opiate can be used to describe those opioids that are alkaloids, derived from the opium poppy; these include morphine and codeine. Opioids include semi-synthetic opiates, i.e., drugs that are synthesized from naturally occurring opiates (such as heroin from morphine and oxycodone from thebaine), as well as synthetic opioids such as methadone, fentanyl, and propoxyphene.

— "Opioids and the Treatment of Chronic Pain: Controversies, Current Status,
and Future Directions" in Experimental and clinical psychopharmacology [17]

About the existing citations:

The lead sentence says, "Opioids are substances that act on the nervous system in a similar way to opiates such as morphine and codeine." The cited source[18] says, "Opiates are drugs derived from opium and include morphine, codeine, and the semi-synthetic derived from them and thebaine." but continues, "The term opioid applies to all agonists and antagonists with morphine like activity, and also naturally occurring and synthetic opioid peptides." Opiates are agonists, therefore opioids includes opiates.

The cited D'Arcy's chapter "4. Opioid Medications for Cancer Pain"[19] defines opiates and opioids as mutually exclusive. Otherwise she never uses the term opiate, but refers to morphine as an opioid: "Some of the opioids are used in their natural form such as morphine and heroin," (p. 56) and "...there are many more formulations of opioids to use for analgesia than morphine." (p. 55)

Taber's Dictionary distinguishes opiate/opioid exclusively but also lists (includes only) "opiate receptors" while Wikipedia, including this article's lead, uses the modern term "opioid receptor". Taber's was certainly cited in good faith, but in this case the source seems dated.

Forgive my loquacity. — Box73 (talk) 14:27, 9 February 2016 (UTC)

  1. ^ a b c D'Arcy, Pamela Stitzlein Davies, Yvonne (2012). Compact clinical guide to cancer pain management an evidence-based approach for nurses. New York: Springer. p. 55. ISBN 9780826109743.{{cite book}}: CS1 maint: multiple names: authors list (link)
  2. ^ Mehdi B (2008). "Opioid analgesics and antagonists". Textbook Of Pharmacology. Elsevier India. p. III.137. ISBN 9788131211588. {{cite book}}: Unknown parameter |editors= ignored (|editor= suggested) (help)
  3. ^ "opioid". Taber's Online Medical Dictionary. Unbound Medicine, Inc. Retrieved 2 September 2015.
  4. ^ Hemmings, Hugh C.; Egan, Talmage D. (2013). Pharmacology and Physiology for Anesthesia: Foundations and Clinical Application: Expert Consult - Online and Print. Elsevier Health Sciences. p. 253. ISBN 1437716792. Opiate is the older term classically used in pharmacology to mean a drug derived from opium. Opioid, a more modern term, is used to designate all substances, both natural and synthetic, that bind to opioid receptors (including antagonists).
  5. ^ Offermanns, Stefan (2008). Encyclopedia of Molecular Pharmacology. Vol. 1 (2 ed.). Springer Science & Business Media. p. 903. ISBN 9783540389163. In the strict sense, opiates are drugs derived from opium and include the natural products morphine, codeine, thebaine and many semi-synthetic congeners derived from them. In the wider sense, opiates are morphine-like drugs with non peptidic structures. The older term opiates is now more and more replaced by the term opioids which applies to any substance, whether endogenous or synthetic, peptidic or non-peptidic, that produces morphine-like effects through action on opioid receptors.
  6. ^ Freye, Enno (2008). "Part II. Mechanism of action of opioids and clinical effects". Opioids in Medicine: A Comprehensive Review on the Mode of Action and the Use of Analgesics in Different Clinical Pain States. Springer Science & Business Media. p. 85. ISBN 9781402059476. Opiate is a specific term that is used to describe drugs (natural and semi-synthetic) derived from the juice of the opium poppy. For example morphine is an opiate but methadone (a completely synthetic drug) is not. Opioid is a general term that includes naturally occurring, semi-synthetic, and synthetic drugs, which produce their effects by combining with opioid receptors and are competively antagonized by nalaxone. In this context the term opioid refers to opioid agonists, opioid antagonist, opioid peptides, and opioid receptors.
  7. ^ Benzon, Honorio; Raja, Srinivasa N.; Fishman, Scott E.; Liu, Spencer; Cohen, Steven P. (2011). Essentials of Pain Medicine. Elsevier Health Sciences. p. 85. ISBN 1437735932.
  8. ^ Stromgaard, Kristian; Krogsgaard-Larsen, Povl; Madsen, Ulf (2009). Textbook of Drug Design and Discovery, Fourth Edition. CRC Press. ISBN 9781439882405.
  9. ^ "Status and Trend Analysis of Illict [sic] Drug Markets". World Drug Report 2015 (PDF). Retrieved 26 June 2015.
  10. ^ "Report III: FDA Approved Medications for the Treatment of Opiate Dependence: Literature Reviews on Effectiveness & Cost- Effectiveness, Treatment Research Institute". Advancing Access to Addiction Medications: Implications for Opioid Addiction Treatment. p. 41.
  11. ^ Hemmings, Hugh C.; Egan, Talmage D. (2012-12-06). Pharmacology and Physiology for Anesthesia: Foundations and Clinical Application. Elsevier Health Sciences. ISBN 1455737933.
  12. ^ Offermanns, Stefan. Encyclopedia of Molecular Pharmacology. Springer Science & Business Media. ISBN 9783540389163.
  13. ^ Freye, Enno (2008-03-12). Opioids in Medicine: A Comprehensive Review on the Mode of Action
    and the Use of Analgesics in Different Clinical Pain States
    . Springer Science & Business Media. ISBN 9781402059476.
  14. ^ Julien, Robert M.; Advokat, Claire D.; Comaty, Joseph E. (2010-10-08). Primer of Drug Action. Macmillan. ISBN 9781429233439.
  15. ^ Herron, Abigail; Brennan, Timothy K. (2015-03-18). The ASAM Essentials of Addiction Medicine. Lippincott Williams & Wilkins. ISBN 9781496310675.
  16. ^ Wikler, A.; Martin, W. R.; Pescor, F. T.; Eades, C. G. (1963-10-24). "Factors Regulating Oral Consumption of an Opioid (Etonitazene) by Morphine-Addicted Rats". Psychopharmacologia. 5: 55–76. PMID 14082382.
  17. ^ Rosenblum, Andrew; Marsch, Lisa A.; Joseph, Herman; Portenoy, Russell K. (2008-10-01). "Opioids and the Treatment of Chronic Pain: Controversies, Current Status, and Future Directions". Experimental and clinical psychopharmacology. 16 (5): 405–416. doi:10.1037/a0013628. ISSN 1064-1297. PMC 2711509. PMID 18837637.
  18. ^ Seth (2009-11-18). Textbook Of Pharmacology. Elsevier India. ISBN 9788131211588.
  19. ^ ARNP, Pamela Davies MS; CNS, Yvonne D'Arcy MS, CRNP (2012-09-26). Compact Clinical Guide to Cancer Pain Management: An Evidence-Based Approach for Nurses. Springer Publishing Company. ISBN 9780826109743.{{cite book}}: CS1 maint: multiple names: authors list (link)

---------------------------------------------

Opioids are drugs and endogenous substances that produce effects like morphine, principally in the central nervous system, by acting on opioid receptors. In a medical context the term usually indicates medications that are artificially made rather than extracted from opium.[2]Common examples include oxycodone, hydrocodone, and hydromorphone.[3] Opioids are primarily used in medicine for the treatment of pain.

Opioids are all drugs and endogenous substances that act on opioid receptors to produce morphine-like effects. It is replacing an older term opiates, which refers to refers to natural (and some sources say semisynthetic) derivatives of opium, such as morphine. Opioids principally act on the central nervous system; Opioid drugs are are primarily used medically for the relief of pain, and recreationally, at significant risk of addiction and overdose.

The citation to D'Arcy's chapter "Opioid Medications for Cancer Pain" distinguishes between opiates and opioids as mutually exclusive, after which she discards "opiate" repeatedly refers to morphine as an "opioid". Even the chapter title uses the umbrella term.

The lead definition of opioid should be replaced. It does not reflect the predominant definition which includes all such substances, including opiates. which is an umbrella term that includes drugs classified as opiates. The current lead definition belongs in the discussion of various definitions, replaced by the modern definition.

I am revising it to:

Opioids are all drugs and endogenous substances that act on opioid receptors to produce morphine-like effects. It includes opiates, an older term that refers to such drugs derived from opium, including morphine itself. Opioid drugs are predominantly central nervous system agents, most often used medically to relieve pain.

The lead sentence says, "Opioids are substances that act on the nervous system in a similar way to opiates such as morphine and codeine." The cited source says, "Opiates are drugs derived from opium and include morphine, codeine, and the semi-synthetic derived from them and thebaine." but continues, "The term opioid applies to all agonists and antagonists with morphine like activity, and also naturally occurring and synthetic opioid peptides." Opiates are agonists, therefore opioids includes opiates.

The citation to D'Arcy's chapter "4. Opioid Medications for Cancer Pain" defines opiates and opioids as mutually exclusive. She never uses the term opiate again but refers to morphine as an opioid: "Some of the opioids are used in their natural form such as morphine and heroin," (p. 56)) and "...there are many more formulations of opioids to use for analgesia than morphine." (p. 55)

Taber's Dictionary distinguishes the two but also lists (includes only) "opiate receptors" while Wikipedia, including the lead, uses the modern term "opioid receptor".

I cite the following:

Opiate is the older term classically used in pharmacology to mean a drug derived from opium. Opioid, a more modern term, is used to designate all substances, both natural and synthetic, that bind to opioid receptors (including antagonists). (p 253)

— Pharmacology and Physiology for Anesthesia: Foundations and Clinical Application [1]

In the strict sense, opiates are drugs derived from opium and include the natural products morphine, codeine, thebaine and many semi-synthetic congeners derived from them. In the wider sense, opiates are morphine-like drugs with non peptidic structures. The older term opiates is now more and more replaced by the term opioids which applies to any substance, whether endogenous or synthetic, peptidic or non-peptidic, that produces morphine-like effects through action on opioid receptors. (p 903)

Encyclopedia of Molecular Pharmacology [2]

...Opiate is a specific term that is used to describe drugs (natural and semi-synthetic) derived from the juice of the opium poppy. For example morphine is an opiate but methadone (a completely synthetic drug) is not. Opioid is a general term that includes naturally occurring, semi-synthetic, and synthetic drugs, which produce their effects by combining with opioid receptors and are competively antagonized by nalaxone. In this context the term opioid refers to opioid agonists, opioid antagonist, opioid peptides, and opioid receptors. (p. 85)

— Opioids in Medicine: A Comprehensive Review on the Mode of Action
and the Use of Analgesics in Different Clinical Pain States
[3]

An opiate, strictly defined, is a drug extracted from the exudate of the poppy. Therefore the term is restricted to two drugs found in the exudates: morphine and codeine. An opioid is any exogenous drug (natural, semisynthetic, or synthetic) that binds to an opiate receptor and produces agonistic, or morphinelike, effects. (p. 322)

— Primer of Drug Action [4]

Opiates are drugs derived from opium, the extract of the seeds of the opium poppy, and include morphine, codeine, and heroin. The term opioid is more comprehensive and includes all agonists and antagonists with morphine-like activity, including natural opiates, semisynthetic drugs such as hydrocodone and hydromorphone, and synthetic drugs, such as oxycodone, methadone, buprenorphine, and fentanyl.

— The ASAM Essentials of Addiction Medicine [5]

Dopamine reuptake via DAT provides the primary mechanism which clears dopamine from synapses in subcortical structures. However, because DAT is spare in the prefrontal cortex, dopamine clearance occurs by extrasynaptic diffusion and ultimately uptake by norepinephrine transporters as well as uptake2 by plasma membrane monoamine transporter and degradation by catechol-O-methyltransferase. [6]

Dopamine reuptake via DAT provides the primary mechanism which clears dopamine from synapses in subcortical structures. However, DAT is spare in the prefrontal cortex so dopamine clearance there occurs by extrasynaptic diffusion and ultimately uptake by the norepinephrine transporter as well as uptake2 with degradation by catechol-O-methyltransferase.[7][6]

from which other transporters sequester DA and NE into vesicles for later storage and release or

Dopamine reuptake via DAT provides the primary mechanism which clears dopamine from synapses in subcortical structures. However, DAT expression is spare in the prefrontal cortex so dopamine clearance there occurs by other mechanisms (i.e.,extrasynaptic diffusion and ultimately uptake by the norepinephrine transporter as well as uptake2 with degradation by catechol-O-methyltransferase).[7][6]

note: There is evidence that dopamine captured by NET may be stored and later released. Other evidence suggests dopamine may be produced as a co-transmitter within cortical norandrenergic projections.

-----

Once in the synapse, dopamine binds to and activates dopamine receptors. These can be the D2Lh type, located on the postsynaptic target cells or the D2Sh autoreceptor type located on the membrane of the presynaptic cell.[8] After an action potential, the dopamine molecules quickly become unbound from their receptors. In subcortical regions they are then absorbed back into the presynaptic cell, via reuptake mediated either by the dopamine transporter or by the plasma membrane monoamine transporter.[20] Once back in the cytosol, dopamine can either be broken down by a monoamine oxidase or repackaged into vesicles by VMAT2, making it available for future release.[18]

However few dopamine transporters exist in the prefrontal cortex allowing the unbound dopamine to diffuse beyond the original synapse. It may be taken up by norepinephrine transporters in adjacent norandrenergic terminals (and likewise broken down by monoamine oxidase) or is catabolized by catechol-O-methyltransferase

However few dopamine transporters exist in the prefrontal cortex allowing the unbound dopamine to diffuse beyond the synapse, where it is free to act until it is either degraded by catechol-O-methyltransferase or is taken up by a norepinephrine transporter in a norandrenergic terminal

It may be taken up by norepinephrine transporters in adjacent norandrenergic terminals (and likewise broken down by monoamine oxidase) or is catabolized by catechol-O-methyltransferase

However few dopamine transporters exist in the prefrontal cortex, allowing the unbound dopamine to diffuse outside the synapse until either removed by norepinephrine transporters in norandrenergic terminals or degraded by extracellular catechol-O-methyltransferase.[8] Some evidence suggests that norandrenergic neurons projecting into the prefrontal cortex may release dopamine as well as norepinephrine.[9][10]

https://books.google.com/books?id=cWbYxSfKN3cC&pg=PA545&lpg=PA545#v=onepage&q&f=false

p 544-6 

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2430672/

http://bmcneurosci.biomedcentral.com/articles/10.1186/1471-2202-6-31

Dopamine also activates α1, β1 and β2 adrenergic receptors.[11][12] At these sites dopamine acts as a cardiac stimulant and vasopressor. α2 At β1 receptors dopamine increases heart rate and force while at α

benzedrine

Because that would overwhelm the field, and those brands aren't significant. Alternatively, consider amitriptyline and doxepin. Elavil and Sinequin (respectively) are listed but both brands are discontinued.

I get your reasoning and desire to keep this focused. Benzedrine belongs because it is established in our vocabulary. It is listed in Oxford and Merriam-Webster Dictionaries. The 2012 Atlantic article, The Lost World of Benzedrine. This isn't true of Alentol, Psychoton or Simpamina. This makes it a special case belonging there. Is there a way to distinguish it in the list without causing clutter or undue attention? — ~~~~

onset[13][14]

response re benzyl methyl carbinamine

(we don't include the majority of amphetamine synonyms ( http://www.commonchemistry.org/ChemicalDetail.aspx?ref=300-62-9 ). I've removed the term and redirected Benzyl methyl carbinamine here since it doesn't seem to be widely used or notable)

I appreciate that there is a difference of opinion.

α-methylphenethylamine is the best synonym largely because it was the source of the term amphetamine There are many other synonyms of amphetamine, more than could or should be listed, yet my addition was not capricious. Benzyl methyl carbinamine was the original synonym used in the 1930s. It is notable that Alles derived "Benzedrien" by combining "BENZyl methyl carbinamine" with "ephEDRINE".[15] For the first several years benzyl methyl carbinamine was widely used to identify the drug, typically parenthetically following Benzedrine. In fact, "amphetamine" was little used originally.

The American Chemical Society database at Common Chemistry is a reliable source but not the gatekeeper of acceptable synonyms. Benzyl methyl carbinamine is listed elsewhere.[16] Wide usage exists in early medical literature—secondary sources concerning the name.[17][18][19][20][21][22][23] Benzyl methyl carbinamine is not trivial. The term was used by the process inventor (Alles), manufacturer (SK&F), and notable physicians such as Bradley reporting his discovery treating attentional disorders.[15][24][25] (β-phenylisopropylamine was another early term encountered.[26])

Wikipedia editors are encouraged to develop drug infoboxes and the field "synonyms" currently lists but a single term. Benzyl methyl carbinamine is historically notable and widely used, and is reasonable to include. Pending any remaining objections, the deletion should be reverted with improved citations (1 or 2). — Box73 (talk) 03:06, 13 January 2016 (UTC)

References

  1. ^ Hemmings, Hugh C.; Egan, Talmage D. (2012-12-06). Pharmacology and Physiology for Anesthesia: Foundations and Clinical Application. Elsevier Health Sciences. ISBN 1455737933.
  2. ^ Offermanns, Stefan. Encyclopedia of Molecular Pharmacology. Springer Science & Business Media. ISBN 9783540389163.
  3. ^ Freye, Enno (2008-03-12). Opioids in Medicine: A Comprehensive Review on the Mode of Action
    and the Use of Analgesics in Different Clinical Pain States
    . Springer Science & Business Media. ISBN 9781402059476.
  4. ^ Julien, Robert M.; Advokat, Claire D.; Comaty, Joseph E. (2010-10-08). Primer of Drug Action. Macmillan. ISBN 9781429233439.
  5. ^ Herron, Abigail; Brennan, Timothy K. (2015-03-18). The ASAM Essentials of Addiction Medicine. Lippincott Williams & Wilkins. ISBN 9781496310675.
  6. ^ a b c Käenmäki, Mikko; Tammimäki, Anne; Myöhänen, Timo; Pakarinen, Kaisa; Amberg, Carolina; Karayiorgou, Maria; Gogos, Joseph A.; Männistö, Pekka T. (1 September 2010). "Quantitative role of COMT in dopamine clearance in the prefrontal cortex of freely moving mice". Journal of Neurochemistry. 114 (6): 1745–1755. doi:10.1111/j.1471-4159.2010.06889.x. ISSN 1471-4159. PMID 20626558. [I]n the mouse, PFC COMT contributes about one half of the total DA clearance.
  7. ^ a b Morón, Jose A.; Brockington, Alicia; Wise, Roy A.; Rocha, Beatriz A.; Hope, Bruce T. (15 January 2002). "Dopamine uptake through the norepinephrine transporter in brain regions with low levels of the dopamine transporter: evidence from knock-out mouse lines". The Journal of Neuroscience. 22 (2): 389–395. ISSN 1529-2401. PMID 11784783. [W]hereas dopamine uptake in caudate and nucleus accumbens depends primarily on the DAT, dopamine uptake in frontal cortex depends primarily on the NET.
  8. ^ Stahl, Stephen M. (2008-03-27). Stahl's Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. Cambridge University Press. pp. 544–46. ISBN 9780521857024.
  9. ^ Devoto, Paola; Flore, Giovanna (2006-04-01). "On the Origin of Cortical Dopamine: Is it a Co-Transmitter in Noradrenergic Neurons?". Current Neuropharmacology. 4 (2): 115–125. ISSN 1570-159X. PMC 2430672. PMID 18615131.
  10. ^ Devoto, Paola; Flore, Giovanna; Saba, Pierluigi; Fà, Mauro; Gessa, Gian (2005-05-02). "BMC Neuroscience". BMC Neuroscience. 6 (1). doi:10.1186/1471-2202-6-31. PMC 1134661. PMID 15865626.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  11. ^ Moses, Scott. "Dopamine". Family Practice Notebook. Retrieved 2016-02-01. Dopamine binds to alpha-1 and beta-1 adrenergic receptors. Mediated through myocardial beta-1 adrenergic receptors, dopamine increase heart rate and force, thereby increasing cardiac output. Alpha-1 adrenergic receptor stimulation on vascular smooth muscle, leads to vasoconstriction and results in an increase in systemic vascular resistance
  12. ^ Katritsis, Demosthenes G.; Gersh, Bernard J.; Camm, A. John (2013-09-19). Clinical Cardiology: Current Practice Guidelines. OUP Oxford. p. 314. ISBN 9780191508516. Dopamine binds to beta-1, beta-2, alpha-1 and dopaminergic receptors.
  13. ^ "Adderall XR, Adderall (amphetamine/dextroamphetamine) dosing, indications, interactions, adverse effects, and more". Medscape. Retrieved 21 January 2016. Onset of action: 30-60 min
  14. ^ Moses, Scott. "Dextroamphetamine". Family Practice Notebook. Retrieved 21 January 2016. (Adderall) Onset of activity: 30 to 60 minutes
  15. ^ a b Francisco, Center for Neurobiology and Psychiatry University of California Samuel H. Barondes Jeanne and Sandford Robinson Professor and Director, San (2003-06-16). Better than Prozac : Creating the Next Generation of Psychiatric Drugs: Creating the Next Generation of Psychiatric Drugs. Oxford University Press, USA. pp. 62–63. ISBN 9780198034506.{{cite book}}: CS1 maint: multiple names: authors list (link)
  16. ^ "NTP-CERHR: Chemicals - Amphetamines". wf1-ext-vip.niehs.nih.gov. Retrieved 2016-01-13.
  17. ^ BYRNE, HARRY V. (1933-11-23). "The Use of Benzyl-Methyl-Carbinamine-Carbonate in the Treatment of Rhinitis". New England Journal of Medicine. 209 (21): 1048–1051. doi:10.1056/NEJM193311232092106. ISSN 0028-4793.
  18. ^ "The effects of toxic doses of benzyl methyl carbinamine (benzedrine) in man". Journal of the American Medical Association. 110 (3): 206–207. 1938-01-15. doi:10.1001/jama.1938.62790030001010. ISSN 0002-9955.
  19. ^ "The effect of benzedrine sulfate (benzyl methyl carbinamine) upon the report of boredom and other factors. - ProQuest". search.proquest.com. Retrieved 2016-01-12.
  20. ^ Molitch, Matthew; Sullivan, John P. (1937-10-01). "The Effect of Benzedrine Sulfate on Children Taking the New Stanford Achievement Test*". American Journal of Orthopsychiatry. 7 (4): 519–522. doi:10.1111/j.1939-0025.1937.tb05294.x. ISSN 1939-0025.
  21. ^ ULRICH, HELMUTH; TRAPP, CARL E.; VIDGOFF, BEN (1936-03-01). "THE TREATMENT OF NARCOLEPSY WITH BENZEDRINE SULPHATE*". Annals of Internal Medicine. 9 (9): 1213–1221. doi:10.7326/0003-4819-9-9-1213. ISSN 0003-4819.
  22. ^ "Human autonomic pharmacology - American Heart Journal". www.ahjonline.com. Retrieved 2016-01-12.
  23. ^ Flexner, James; Bruger, Maurice; Wright, Irving S. (1938-02-01). "Autonomic Drugs and the Biliary System I. the Action of Acetyl-B-Methyl Choline Chloride (mecholyl) and Benzyl Methyl Carbinamine Sulphate (benzedrine Sulphate) on the Gall Bladder". Journal of Pharmacology and Experimental Therapeutics. 62 (2): 174–178. ISSN 1521-0103.
  24. ^ "Harvard Medical Alumni Bulletin, 1934, Volume 9, Page 3 | Document Viewer". Mocavo. Retrieved 2016-01-13.
  25. ^ Bradley, Charles; Bowen, Margaret (1941-01-01). "Amphetamine (benzedrine) Therapy of Children's Behavior Disorders*". American Journal of Orthopsychiatry. 11 (1): 92–103. doi:10.1111/j.1939-0025.1941.tb05781.x. ISSN 1939-0025.
  26. ^ "dl-beta-Phenylisopropylamine (Amphetamine) and Related Compounds - [www.rhodium.ws]". www.erowid.org. Retrieved 2016-01-13.

I appreciate that there is a difference of opinion. Here is my reasoning:

  1. c. 1932-1946 the common trivial name was benzedrine not amphetamine. (note lower case "b".) Just like amphetamine, benzedrine is a contraction of a systemic name plus the known congener: benzedrine = benzyl methyl carbinamine + ephedrine = benz+edrine)[1] ("amphetamine" was convened by a party of the AMA; "benzedrine" was by Gordon Alles.)
  2. c. 1932-1946 The name "benzyl methyl carbinamine" enjoyed wide-spread use alone or following benzedrine in journal articles and pharmaceutical advertisements.[2][3][4][5][6][7][8][9] inclusion in a list of amphetamine synonyms.[10] historical SKF documents including blueprint of factory producing benzyl methyl carbinamine[11]
  3. The amphetamine article encompasses not just scientific but also historic perspectives. This synonym is historically notable.
  4. It is common for drugs to include several synonyms. For example methamphetamine has 3, aspirin has 4. 
  5. One way to improve articles is to add information to infoboxes in drug articles.
  6. The American Chemical Society database in "Common Chemistry" is certainly a reliable source but it is neither absolutely comprehensive nor the final judge of valid synonyms.
  7. Let's be fair. Substituted amphetamines doesn't seem to be widely used per Wikipedia's definition. 

Forgetting all the brand names, and street names, there are way too many amphetamine chemical synonyms to reasonably list. There has to be restraint and discrimination. But the template's plural "synonyms" provides for a reasonable few. I believe benzyl methyl carbinamine is a reasoned choice, not simply a spaceholder. It is the original conventional chemical name of amphetamine, something I didn't know a month ago. (There should be no necessity of a third term but three seems a reasonable limit.)

Now, if only benzyl methyl carbinamine would fit on a single line!


While enantiopure dextromethamphetamine is a more potent drug than racemic methamphetamine, the racemic form is sometimes produced and sold instead of dextromethamphetamine due to the relative ease of its synthesis by certain methods and the limited availability of associated chemical precursors.

benzyl methyl carbinamine[12]

N-methyl-alpha-methylphenethylamine

New citation test[13][14]

  1. Severe overdose / CNS, add generalized tonic-clonic seizures.[15][16][17][18][19] Seizures are uncommon with mild to moderate overdose but occur with large, severe overdose. The first two citations should be sufficient; the third is a good secondary source.
  2. Seppi may be interested in this related item: The Nucleus Accumbens: A Comprehensive Review.[20]

References

  1. ^ Francisco, Center for Neurobiology and Psychiatry University of California Samuel H. Barondes Jeanne and Sandford Robinson Professor and Director, San (2003-06-16). Better than Prozac : Creating the Next Generation of Psychiatric Drugs: Creating the Next Generation of Psychiatric Drugs. Oxford University Press, USA. pp. 62–63. ISBN 9780198034506.{{cite book}}: CS1 maint: multiple names: authors list (link)
  2. ^ BYRNE, HARRY V. (1933-11-23). "The Use of Benzyl-Methyl-Carbinamine-Carbonate in the Treatment of Rhinitis". New England Journal of Medicine. 209 (21): 1048–1051. doi:10.1056/NEJM193311232092106. ISSN 0028-4793.
  3. ^ "The effects of toxic doses of benzyl methyl carbinamine (benzedrine) in man". Journal of the American Medical Association. 110 (3): 206–207. 1938-01-15. doi:10.1001/jama.1938.62790030001010. ISSN 0002-9955.
  4. ^ "The effect of benzedrine sulfate (benzyl methyl carbinamine) upon the report of boredom and other factors. - ProQuest". search.proquest.com. Retrieved 2016-01-12.
  5. ^ Molitch, Matthew; Sullivan, John P. (1937-10-01). "The Effect of Benzedrine Sulfate on Children Taking the New Stanford Achievement Test*". American Journal of Orthopsychiatry. 7 (4): 519–522. doi:10.1111/j.1939-0025.1937.tb05294.x. ISSN 1939-0025.
  6. ^ ULRICH, HELMUTH; TRAPP, CARL E.; VIDGOFF, BEN (1936-03-01). "THE TREATMENT OF NARCOLEPSY WITH BENZEDRINE SULPHATE*". Annals of Internal Medicine. 9 (9): 1213–1221. doi:10.7326/0003-4819-9-9-1213. ISSN 0003-4819.
  7. ^ "Harvard Medical Alumni Bulletin, 1934, Volume 9, Page 3 | Document Viewer". Mocavo. Retrieved 2016-01-12.
  8. ^ "Human autonomic pharmacology - American Heart Journal". www.ahjonline.com. Retrieved 2016-01-12.
  9. ^ Flexner, James; Bruger, Maurice; Wright, Irving S. (1938-02-01). "Autonomic Drugs and the Biliary System I. the Action of Acetyl-B-Methyl Choline Chloride (mecholyl) and Benzyl Methyl Carbinamine Sulphate (benzedrine Sulphate) on the Gall Bladder". Journal of Pharmacology and Experimental Therapeutics. 62 (2): 174–178. ISSN 1521-0103.
  10. ^ "NTP-CERHR: Chemicals - Amphetamines". wf1-ext-vip.niehs.nih.gov. Retrieved 2016-01-12.
  11. ^ "Wellcome Library Western Manuscripts and Archives catalogue". archives.wellcomelibrary.org. Retrieved 2016-01-12.
  12. ^ Smith, Kline & French Laboratories (1934). "For Shrinking Nasal Mucosa Benzedrine Solution Inhaler [advertisement]" (JPEG). Harvard Medical Alumni Bulletin. 9. Boston: 2. Retrieved 6 January 2016. A glance at the formula of Benzedrine (benzyl methyl carbinamine) shows that it has the fundamental grouping which causes shrinkage of nasal mucosa. {{cite journal}}: |archive-date= requires |archive-url= (help)
  13. ^ Heal, David J; Smith, Sharon L; Gosden, Jane; Nutt, David J (2013-06-01). "Amphetamine, past and present – a pharmacological and clinical perspective". Journal of Psychopharmacology (Oxford, England). 27 (6): 479–496. doi:10.1177/0269881113482532. ISSN 0269-8811. PMC 3666194. PMID 23539642. The intravenous use of d-amphetamine and other stimulants still pose major safety risks to the individuals indulging in this practice. Some of this intravenous abuse is derived from the diversion of ampoules of d-amphetamine, which are still occasionally prescribed in the UK for the control of severe narcolepsy and other disorders of excessive sedation.
  14. ^ Bett, W. R. (1946-08-01). "Benzedrine Sulphate in Clinical Medicine: A Survey of the Literature". Postgraduate Medical Journal. 22 (250): 210. ISSN 0032-5473. PMC 2478360. PMID 20997404. Reifenstein and Davidoff used intravenous injections of 10 to 40 mg. of benzedrine to terminate amytal narcosis.... Michelsen and Verlot overcame narcosis and the depressor effects of avertin anaesthesia by injecting 20 mg. of benzedrine sulphate. Boyd, administering 10 mg. dissolved in 1 c.c. distilled water intravenously to 12 children after avertin anaesthesia, obtained as the only immediate effect a return of the superficial reflexes.
  15. ^ Brown, J. William L.; Dunne, John W.; Fatovich, Daniel M.; Fatovic, Daniel M.; Lee, Judy; Lawn, Nicholas D. (2011-02-01). "Amphetamine-associated seizures: clinical features and prognosis". Epilepsia. 52 (2): 401–404. doi:10.1111/j.1528-1167.2010.02924.x. ISSN 1528-1167. PMID 21314677.
  16. ^ Derlet, R. W.; Albertson, T. E.; Rice, P. (1990-03-01). "Protection against d-amphetamine toxicity". The American Journal of Emergency Medicine. 8 (2): 105–108. ISSN 0735-6757. PMID 2302276.
  17. ^ "Drug Use and Dependence - Amphetamines". Merck Manuals Professional Edition. Retrieved 2015-12-26.
  18. ^ Alldredge, B. K.; Lowenstein, D. H.; Simon, R. P. (1989-08-01). "Seizures associated with recreational drug abuse". Neurology. 39 (8): 1037–1039. ISSN 0028-3878. PMID 2788249.
  19. ^ Derlet, R. W.; Albertson, T. E.; Rice, P. (1990-08-01). "Antagonism of cocaine, amphetamine, and methamphetamine toxicity". Pharmacology, Biochemistry, and Behavior. 36 (4): 745–749. ISSN 0091-3057. PMID 2217500.
  20. ^ Salgado, Sanjay; Kaplitt, Michael G. (2015-02-18). "The Nucleus Accumbens: A Comprehensive Review". Stereotactic and Functional Neurosurgery. 93 (2): 75–93. doi:10.1159/000368279. ISSN 1423-0372. PMID 25720819.


These represent the current brands in the United States, except Adderall which is discontinued but available generically.[1][2] Dexedrine was available in 1937 as an instant release tablet, which is discontinued but available as Zenzedi and generically;[3][4] Dexedrine listed here represents the extended release "Spansule" capsule which was approved in 1976.[5][6] Amphetamine sulfate tablets, now sold as Evekeo (brand), were originally sold as Benzedrine (brand) sulfate in 1935[7][8] and discontinued sometime after 1976.[9] Vyvanse and Dyanavel are only available as brand pharmaceuticals, due to the patented mechanisms used to release the active amphetamine ingredient.

Severe overdose / CNS, add generalized tonic-clonic seizures. [10][11][12] Seizures are uncommon with mild to moderate overdose but occur with large, severe overdose.

Amphetamine[13]

Consider changing hyperpyrexia to hyperthermia which is the

All contain dextroamphetamine sulfate, which obviously is equal. Amphetamine sulfate and dextroamphetamine sulfate are considered equal in drug monographs. The other salts in Adderall have a higher molecular weight, which is noted in pharmaceutical literature, and this effects the amount of base and the potency. This is considered in pulished research, such as the base content comparison quoted in the research below.

Concerning equipotent daily doses with lisdexamfetamine.

After administration of a single LDX [lisdexamfetamine] dose of 70 mg under three dose conditions (fasting and with capsule only; fasting and with solution containing capsule contents; and intact capsule after a high-fat meal), systemic exposure of d-amphetamine was bioequivalent, as measured by drug plasma concentration-time plots and maximum drug concentration. The 70-mg dose is expected to be therapeutically equivalent to the amphetamine base content of 30-mg MAS-XR (20.8 mg vs. 18.8 mg, respectively), which is known to be therapeutically active in children with ADHD.[14]

This agrees with the template, excepting that the study used the nearest manufactured dose unit for practical purposes. They make this clear noting the base content is 20.8mg vs, 18.8mg (lisdexamfetamine vs. Adderall). (MAS is Mixed Amphetamine Salts; used because Adderall is a brand-name; However Adderall is used in Wikipedia.}.The template uses exactly equal base amounts, resulting in 35mg Adderall XR = 74mg lisdexamfetamine..(The range for Adderall, amphetamine sulfate and amphetamine base suspension addressed a concern by one editor that pure stimulant effects of dextroamphetamine are 4 times stronger than levoamphetamine. In treatment for ADHD the two enantiomers are considered equally potent, as is evident in the cited source above.) By keeping the base content exactly equal allowed all of the form to coexist in the template.

A concern was raised about food effecting the pharmacokinetics of lisdexamfetamine. No significant effect was found.[15]

link 1[16] link 2[17] link 3[18] link 4[19]

[20]


[21]

Merck[22]

Big Boy 14 foot [23]

Tony Matar Big Boy[24][25]

Norco Big Boy[26][27]

Covering a number of issues[28][29]

Routes of administration: Since Benzedrine inhalers are long gone, nasal inhalation should be eliminated from Medical, or somehow qualified.

Metabolism. I'm confused between "amphetamine only" and "other". Does "other" mean active metabolites?

Onset of action: This gets into medical vs recreational distinctions as well as site of action (central vs nasal). 

  1. We need to divide IR into oral and intranasal/intravenous. Perhaps IR (oral) and IR (intranasal/intravenous). However since XR refers to oral, and IR tends to be used for oral, keep XR and IR for oral, and isolate intranasal/intravenous. Perhaps IR, XR, IN/IV?
  2. Despite IR standing for immediate release, oral IR effects certainly are not immediate. Immediate only means it isn't a time release / sustained release / extended release formulation. The time to be ingested, absorbed, cross the BBB, accumulate concentrations to cause clinical effect exist.
  3. IR and XR (oral) should both have the same onset since a part of the (larger) XR dose is in IR form.
  4. The reported value for IR oral is 30-60 minutes. (I don't have the references at hand, but they vary by source.)
  5. Although IN or IV is almost immediate, I suggest "rapid" over "immediate". (Also relieves confusion with immediate release.)

Duration of action presents the same issues as onset. I believe the current IR values listed are for oral amphetamine, either Adderall or pure racemic forms. (That is another reason the onset value for IR should be oral.) I am skeptical that these values are for non oral administration (and decongestant effect) which might have different durations and possibly slightly different half-lives (for example, the decongestant is local vs systemic).

Medical. "Amphetamine ... is sometimes prescribed for its past medical indications ... such as ... nasal congestion."

Amphetamine is no longer prescribed for nasal congestion. Currently, psychiatrists sometimes prescribe amphetamine for depression and rheumatologists occasionally for chronic fatigue syndrome. However, the Benzedrine inhalers are long gone and no competent provider would prescribe oral amphetamine (or d-amphetamine) for congestion.

As mentioned, chronic fatigue syndrome might be a potential candidate for notable off-label use. I'm collecting sources and will follow up.

Amphetamine derivatives. The definition of Amphetamine derivatives is right on. As my friend Seppi would guess, my two issues deal with substituted amphetamines: (note: I recognize that this issue is wider than the amphetamine article itself and certainly belongs to the substituted amphetamines article.)

  • It is equating "amphetamines" with "substituted amphetamines". 
  • It is saying both are common terms.
  • It (referring to substituted amphetamines here as derivatives) is meant to recognize/satisfy criticisms (I've raised) while continuing to use it inclusively elsewhere.

"Amphetamines" is a common term and commonly includes amphetamine (and its enantiomers) as well as derivatives. (The extent of the derivatives varies.) "Substituted amphetamines" is not a common term but a somewhat esoteric term and frequently excludes amphetamine and its enantiomers. Its esoteric nature makes it difficult to collect many definitions. (If we search Lithuanian literature, we would find Lithuanian terms to be common, but outside of Lithuanian literature, the Lithuanian terms would be rare. They are esoteric. Should we use Lithuanian literature to demonstrate that the terms are common (i.e., popular) generally? (except in Lithuania.)

At the risk of beating a dead horse, here are my overdue sources dealing with substituted amphetamines:

Amphetamine is clearly excluded in these quotes from different versions of a classic psychiatry reference:

The classic substituted amphetamines include MDMA, MDEA, 2,5-dimethoxy-4-methylamphetamine (DOM, STP), dimethyltryptamine (DMT), MMDA, and trimethoxyamphetamine (TMA), which are also commonly classified with amphetamines. — Kaplan and Sadock's Pocket Handbook of Clinical Psychiatry [30]

With a few notable exceptions, animals in experimental situations self-administer most of the drugs that humans tend to use and abuse. Included among the drugs are μ- and δ-opioid agonists, cocaine, amphetamine and amphetamine-like agents, substituted amphetamines, such as MDMA, alcohol, barbiturates, many benzodiazepines, a number of volatile gases and vapors (e.g., nitrous oxide and ether), PCP, and nicotine. — Kaplan & Sadock's Comprehensive Textbook of Psychiatry [31]

In the first quote above note that he said, "also commonly classified with amphetamines" not "also commonly classified as amphetamines"   This literally distinguishes amphetamine from substituted amphetamines:  

Amphetamine and substituted amphetamines, including methamphetamine, methylphenidate (Ritalin), methylenedioxymethamphetamine (ecstasy), and the herbs khat and ephedra, encompass the only widely administered class of drugs that predominantly release neurotransmitter, in this case principally catecholamines, by a non-exocytic mechanism. — "Mechanisms of neurotransmitter release by amphetamines: a review" in Progress in Neurobiology [32]

The following text likewise excludes amphetamine from substituted amphetamines. In fact it would exclude not only amphetamine but close congeners such as ephedrine and methamphetamine; this may explain the distinction between "amphetamine-like agents" (or "amphetamine-type stimulants") and "substituted amphetamines" (or Ecstasy) as used in Kaplan.

MDMA is one of a number of closely related substances known as substituted amphetamines.... The substituted amphetamines are entirely synthetic ... in most western countries substituted amphetamines are illegal... Some ecstasy tablets many not contain any substituted amphetamines at all, they may contain methamphetamnine, LSD, ketamine or inert substances. — Drink, Drugs and Dependence: From Science to Clinical Practice [33]

These chapter end questions is Fundamentals of Pharmacology allude to the distinction of amphetamines from MDMA, which is commonly referred to a substituted amphetamine.

3. What is the chemical name for ecstasy? To which class of drugs is it closely related? ... 5 Compare and contrast the effects of ecstasy with those of amphetamines. — Fundamentals of Pharmacology [34]

A Penn State Dept. of Chemistry PowerPoint presentation includes a slide graphic[35] showing amphetamine as the source but excluding it from the class. Note yellow color of title and substituted amphetamines structural diagrams vs red for amphetamine.

Substituted amphetamines is a technical term used by chemists. Similarly substituted morphinans or simply morphinans is a technical term used by chemists which includes morphine and its many congeners. Neither are commonly used. We don't talk about the abuse of prescription (substituted) morphinans. We don't commonly call heroin a (substituted) morphinan. We don't say morphine derivatives are commonly called opioids and (substituted) morphinans. To do so is a promotion of the esoteric term to the level of the common term. Now I can find the term morphinans used by chemists and toxicologists but not in common usage. Chemists and toxicologists use "substituted amphetamines" to include amphetamine itself and all its derivatives. But the term, while a bit more common than morphinans is not common and when applied in medicine and pharmacology is typically not inclusive or not used. By contrast, the term amphetamines is common and always includes amphetamine itself, it almost always includes chemically related stimulants, and frequently MDMA type derivatives with psychedelic properties.

The problem here is, of course that amphetamine is a chemically derived name like barbiturate and benzodiazepine, yet we don't commonly add substituted to them. Looking at other psychoactive drugs, we have the modern term opioid which spans morpinans (which includes opiates) and non-morphinans (which are unrelated structures). (The mutually exclusive meaning of opiate and opioid is passing as opioid becomes the umbrella term.) So opioid has become a functional class. So too antipsychotic, anticonvulsant (or increasingly anti seizure/epilepsy medication), mood stabilizer (which is lithium and many anticonvulsants). Then there are tranquilizer, major tranquilizer, neuroleptic, anti-anxiety medication and so on which are either antiquated or vernacular. These are all functional classes.

The problem here is, of course that amphetamine is a chemically derived name like barbiturate and benzodiazepine, yet we don't commonly add substituted to them. Like amphetamine (unintended pun) we have phenethylamine.(aka phenylethylamine) and cathinone. Both are a substance and a chemical drug class. The substances are not generally encountered as often as amphetamine, in use or language, and the classes occur with and without "substituted". Here again, we see chemists and Wikipedia using substituted X, but commonly just X as the drug class. When substituted X is commonly used, it is exclusive of X: derivatives of X or X with substitutions. So here too the inclusive definition is pretty much common to chemists and Wikipedia. They present the same potential mistranslations as substituted amphetamines, but fewer real linguistic dangers because they aren't commonly encountered (or much less frequently).

Consider the related term substituted cathinone. A recent article Emerging drugs of abuse: current perspectives on substituted cathinones begins: Substituted cathinones are synthetic analogs of cathinone...[36] Like substituted amphetamines, substituted cathiones is generally used to refer to derivatives: in this case so called "bath salts".

In all the medical literature I searched, I never found the term "substituted amphetamine psychosis", "substituted amphetamine dependence" or "substituted amphetamine withdraw", though all of these are true for (and likely more frequent with) methamphetamine, which technically is a substituted amphetamine, and various other amphetamine derivatives.

Inclusive use of "substituted amphetamines".

I have found that toxicologists are those tending to use substituted amphetamines and using it in the inclusive sense. For example James O'Callaghan "Neurotoxic effects of substituted amphetamines in rats and mice" a chapter in Handbook of Neurotoxicology, Vol II and another book titled Neurobiological Mechanisms of Drugs of Abuse: Cocaine, Ibogaine, and Substituted Amphetamines.[37][38] Although the latter is a collection of papers presented at a seminar on drug abuse, substituted amphetamines is only used two articles, one being the chapter/paper co-written by O'Callaghan and the editor. Another toxicologist is George Ricaurte, a controversial anti-drug researcher best known for a retracted article in the journal Science where methamphetamine toxicity was attributed to MDMA.[39] I got the impression that these fellows never met an amphetamine that wasn't toxic and the term "substituted amphetamines" was being used as a melting pot. O'Callaghan for example, concerned about therapeutic doses of amphetamine used in ADHD writes, "[I]t is not uncommon to see all substituted amphetamines labelled as potentially or outright neurotoxic."[40] which he disavows but seems to arrive at anyway by discussing asymptomatic brain changes such as dopamine deficits prior to the presentation of Parkinson's. He and Miller seem rather loquacious, expansive in terms of toxicity, eager to apply rodent research to humans and fond of the term "substituted amphetamines". What I'm saying is "substituted amphetamines" is being used by those with a scientific prejudice or a political agenda, particularly Ricaurte. But all that aside, these toxicologists impress me as predominant published users of "substituted amphetamines" inclusive of amphetamine—Wikipedia and them.

The other issue is what I cannot cite. All of the books, papers and journal articles by credentialed professionals that never use the term substituted amphetamines. All of the physicians that had to take organic chemistry to get into med school who don't use substituted amphetamines or use it differently when they publish. All of the editorial boards who don't promote the term. The lack of letters to JAMA or various neuropsychiatry journals complaining about the ambiguity of the term amphetamines. The term isn't common.

Regarding the template Amphetamine base in marketed amphetamine medications, this was changed from transcluded to substituted on the grounds that two articles are not sufficient reason to transclude a template. After consultation, I can find no Wikipedia policy concerning a minimum number of articles being required for transclusion; this would not be a reason to substitute the template (given two or more articles access the template). Obviously transclusion is more efficient in improving the content. If transclusion is acceptable at Dextroamphetamine, Adderall and Lisdexamfetamine, I can see no reason why it needs to be substituted instead at Amphetamine. Concerns over content effect all articles the template is transcluded in, so transclusion, with discussion and editing at the template itself, would benefit all of these articles.

After reviewing the improvements of syntax and tweaking of references in the substituted copy, most have been incorporated into the base template, the exception being revisions to the syntax of the chemical formulas which would permit the formulas to break. Line breaks in the formulas is confusing and burdensome. Likewise I maintained the heavier dot, as the standard dot is difficult to perceive with some resolutions and for some people.

The substitution raises issues of ownership (WP:OWN) as this would maintain control over a certain article rather than resolving common issues. (How do the changes to the substituted template apply only to the amphetamine article?) Given the previous reasoning and to correct appearances of ownership, the transclusion of the Amphetamine base... template should be restored and improvements shared by all.

References

  1. ^ "Drugs@FDA: FDA Approved Drug Products". U.S. Food and Drug Administration. Retrieved 30 December 2015. Marketing Status: Discontinued
  2. ^ "Determination That Adderall (Amphetamine Aspartate; Amphetamine Sulfate; Dextroamphetamine Saccharate; Dextroamphetamine Sulfate) Tablet and 13 Other Drug Products Were Not Withdrawn From Sale for Reasons of Safety or Effectiveness". Federal Register. 5 November 2013. Retrieved 30 December 2015.
  3. ^ Heal, David J; Smith, Sharon L; Gosden, Jane; Nutt, David J (1 June 2013). "Amphetamine, past and present – a pharmacological and clinical perspective". Journal of Psychopharmacology (Oxford, England). 27 (6): 479–496. doi:10.1177/0269881113482532. ISSN 0269-8811. PMC 3666194. PMID 23539642. Smith, Kline and French synthesised [sic] both isomers, and in 1937 commenced marketing of d-amphetamine, which was the more potent of the two isomers, under the trade name of Dexedrine®.
  4. ^ "Drugs@FDA: FDA Approved Drug Products: Dexedrine". U.S. Food and Drug Administration. Retrieved 30 December 2015. DEXEDRINE ... TABLET;ORAL 5MG Discontinued
  5. ^ "DEXEDRINE - Official Site For DEXEDRINE - DEXEDRINE Spansule - DEXEDRINE Spansules - DEXEDRINE For ADHD". Official Site For DEXEDRINE. Retrieved 30 December 2015.
  6. ^ "Drugs@FDA: Dexedrine: Label and Approval History". U.S. Food and Drug Administration. Retrieved 30 December 2015. 08/02/1976 ... Approval
  7. ^ Strohl, Madeleine P. (2011-03-01). "Bradley's Benzedrine Studies on Children with Behavioral Disorders". The Yale Journal of Biology and Medicine. 84 (1): 27–33. ISSN 0044-0086. PMC 3064242. PMID 21451781. Bradley experimented with Benzedrine sulfate, a drug marketed to doctors by the company Smith, Kline & French (SKF) between 1935 and 1937...
  8. ^ Heal, David J; Smith, Sharon L; Gosden, Jane; Nutt, David J (2013-06-01). "Amphetamine, past and present – a pharmacological and clinical perspective". Journal of Psychopharmacology (Oxford, England). 27 (6): 479–496. doi:10.1177/0269881113482532. ISSN 0269-8811. PMC 3666194. PMID 23539642. Smith, Kline and French introduced Benzedrine onto the market in 1935 as a treatment for narcolepsy (for which it is still used today), mild depression, post-encephalitic Parkinsonism and a raft of other disorders.
  9. ^ Heal, David J; Smith, Sharon L; Gosden, Jane; Nutt, David J (2013-06-01). "Amphetamine, past and present – a pharmacological and clinical perspective". Journal of Psychopharmacology (Oxford, England). 27 (6): 479–496. doi:10.1177/0269881113482532. ISSN 0269-8811. PMC 3666194. PMID 23539642. The use of Benzedrine to treat ADHD declined dramatically after Gross (1976) reported that the racemate was significantly less clinically effective than Dexedrine. Currently, the only use of l-amphetamine in ADHD medications is in mixed salts/mixed enantiomers amphetamine...
  10. ^ Cite error: The named reference :4 was invoked but never defined (see the help page).
  11. ^ Cite error: The named reference :5 was invoked but never defined (see the help page).
  12. ^ Cite error: The named reference :6 was invoked but never defined (see the help page).
  13. ^ United States Congress Senate Committee on the Judiciary Subcommittee to Investigate Juvenile Delinquincy (1 January 1972). Amphetamine legislation 1971: Hearings, Ninety-second Congress, first session, pursuant to S. Res. 32, section 12, investigation of juvenile delinquency in the United States (PDF). U.S. Govt. Print. Off. p. 161. Retrieved 1 January 2016. We made a decision in January of 1969 to cease the manufacture of injectable methamphetamines.
  14. ^ Goodman, David W. (2010-05-01). "Lisdexamfetamine Dimesylate (Vyvanse), A Prodrug Stimulant for Attention-Deficit/Hyperactivity Disorder". Pharmacy and Therapeutics. 35 (5): 273–287. ISSN 1052-1372. PMC 2873712. PMID 20514273.
  15. ^ Krishnan, Suma; Zhang, Yuxin (2008-03-01). "Relative bioavailability of lisdexamfetamine 70-mg capsules in fasted and fed healthy adult volunteers and in solution: a single-dose, crossover pharmacokinetic study". Journal of Clinical Pharmacology. 48 (3): 293–302. doi:10.1177/0091270007310381. ISSN 0091-2700. PMID 18285619.
  16. ^ Schumacher, Mark A.; Basbaum, Allan I.; Way, Walter L. (2012-01-03). "Chapter 31". Basic and Clinical Pharmacology 12/E (12 edition ed.). New York: McGraw-Hill Medical. p. 543. ISBN 9780071764018. {{cite book}}: |edition= has extra text (help)
  17. ^ Strain, Eric C.; Lofwall, Michelle R.; Jaffe, Jerome H. (2009-06-08). "11.10 Opioid-Related Disorders". Kaplan and Sadock's Comprehensive Textbook of Psychiatry (9th edition ed.). Philadelphia, Pa.: LWW. p. 1360. ISBN 9780781768993. The term opioid was coined to include the opiates, which are the naturally occurring drugs derived from opium (morphine and codeine), the semisynthetic drugs produced from opium derivatives, and a wider range of totally synthetic agents bearing little chemical resemblance to morphine. {{cite book}}: |edition= has extra text (help)
  18. ^ Goodman and Gilman's The Pharmacological Basis of Therapeutics, Twelfth Edition (12 edition ed.). New York, NY: McGraw-Hill Education / Medical. 2011-01-10. ISBN 9780071624428. {{cite book}}: |edition= has extra text (help)
  19. ^ Kosten, Thomas R.; George, Tony P. (2002-07-01). "The Neurobiology of Opioid Dependence: Implications for Treatment". Science & Practice Perspectives. 1 (1): 13–20. ISSN 1930-4307. PMC 2851054. PMID 18567959.
  20. ^ Hanson, Shelley (November 26, 2007). "Big Boy Gets His Smile Back". www.theintelligencer.net. Wheeling, WV. Archived from the original on October 15, 2015. Retrieved October 15, 2015. When the giant hamburger it held is atop its hand, the Big Boy is about 14 feet tall. {{cite news}}: More than one of |work= and |website= specified (help); Unknown parameter |subscription= ignored (|url-access= suggested) (help)
  21. ^ Hanson, Shelley (November 26, 2007). "Big Boy Gets His Smile Back". www.theintelligencer.net. Wheeling, WV. When the giant hamburger it held is atop its hand, the Big Boy is about 14 feet tall. {{cite news}}: |access-date= requires |url= (help); |archive-url= requires |url= (help); More than one of |work= and |website= specified (help); Unknown parameter |subscription= ignored (|url-access= suggested) (help)
  22. ^ "Search results for opioid - Merck Manuals Professional Edition". Merck Manuals - Professional Version. Retrieved 2015-10-15.
  23. ^ Hanson, Shelley (November 26, 2007). "Big Boy Gets His Smile Back". The Intelligencer. Wheeling, WV: Ogden Newspapers. Archived from the original on October 15, 2015. Retrieved October 15, 2015. When the giant hamburger it held is atop its hand, the Big Boy is about 14 feet tall.
  24. ^ "USATODAY.com - Restaurateur battles to keep 'Big Boy'". usatoday30.usatoday.com. Retrieved 2015-10-15.
  25. ^ "Big Boy Statue Either Art or Advertising". The Washington Post. 2004-04-18. ISSN 0190-8286. Retrieved 2015-10-15.
  26. ^ "Showdown at the Norco Corral: Big Boy vs. Cowboy Bob". NBC Southern California. Retrieved 2015-10-15.
  27. ^ "Showdown: Norco vs. Bob's Big Boy statue". Retrieved 2015-10-15.
  28. ^ Carter, Lawrence P.; Griffiths, Roland R. (1 December 2009). "Principles of laboratory assessment of drug abuse liability and implications for clinical development". Drug and alcohol dependence. 105S1: S14–S25. doi:10.1016/j.drugalcdep.2009.04.003. ISSN 0376-8716. PMC 2763984. PMID 19443137.
  29. ^ "Prescription Drug Abuse Glossary". National Institute on Drug Abuse. National Institute on Drug Abuse. Retrieved 11 December 2015.
  30. ^ Kaplan and Sadock's Pocket Handbook of Clinical Psychiatry, 5th Edition (Fifth edition ed.). Philadelphia, Pa.: Lippincott Williams and Wilkins. 2010-04-01. p. 135. ISBN 9781605472645. The classic substituted amphetamines include MDMA, MDEA, 2,5-dimethoxy-4-methylamphetamine (DOM, STP), dimethyltryptamine (DMT), MMDA, and trimethoxyamphetamine (TMA), which are also commonly classified with amphetamines. {{cite book}}: |edition= has extra text (help)
  31. ^ Sadock, Benjamin J.; Sadock, Virginia A.; Ruiz, Pedro, eds. (2009). "11.Substance-Related Disorders". Kaplan & Sadock's comprehensive textbook of psychiatry. Vol. 1 (9th ed.). Lippincott Williams & Wilkins. p. 1260. ISBN 0781768993. With a few notable exceptions, animals in experimental situations self-administer most of the drugs that humans tend to use and abuse. Included among the drugs are μ- and δ-opioid agonists, cocaine, amphetamine and amphetamine-like agents, substituted amphetamines, such as MDMA, alcohol, barbiturates, many benzodiazepines, a number of volatile gases and vapors (e.g., nitrous oxide and ether), PCP, and nicotine.
  32. ^ Sulzer, David; Sonders, Mark S.; Poulsen, Nathan W.; Galli, Aurelio (2005-04-01). "Mechanisms of neurotransmitter release by amphetamines: a review" (PDF). Progress in Neurobiology. 75 (6): 406–433. doi:10.1016/j.pneurobio.2005.04.003. ISSN 0301-0082. PMID 15955613.
  33. ^ Rattray, Marcus (2002-05-31). "Chapter 12. Ecstasy". In Caan, Woody; de Belleroche, Jackie (eds.). Drink, Drugs and Dependence: From Science to Clinical Practice (1st edition ed.). London: Routledge. p. 132. ISBN 9780415278911. MDMA is one of a number of closely related substances known as substituted amphetamines.... The substituted amphetamines are entirely synthetic ... in most western countries substituted amphetamines are illegal... Some ecstasy tablets many not contain any substituted amphetamines at all, they may contain methamphetamnine, LSD, ketamine or inert substances. {{cite book}}: |edition= has extra text (help)
  34. ^ Bullock, Shane; Manias, Elizabeth (2013-10-15). "Chapter 25. Drug Abuse in Sport". Fundamentals of Pharmacology (7 edition ed.). Pearson Australia. p. 245. {{cite book}}: |edition= has extra text (help)
  35. ^ "Substituted Amphetamines". research.chem.psu.edu. Retrieved 2015-10-07.
  36. ^ Paillet-Loilier, Magalie; Cesbron, Alexandre; Le Boisselier, Reynald; Bourgine, Joanna; Debruyne, Danièle (2014-01-01). "Emerging drugs of abuse: current perspectives on substituted cathinones". Substance Abuse and Rehabilitation. 5: 37–52. doi:10.2147/SAR.S37257. ISSN 1179-8467. PMC 4043811. PMID 24966713.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  37. ^ Handbook of Neurotoxicology: Volume II (2002 edition ed.). Totowa, NJ: Humana Press. 2002-03-20. ISBN 9780896037960. {{cite book}}: |edition= has extra text (help)
  38. ^ Neurobiological Mechanisms of Drugs of Abuse: Cocaine, Ibogaine, and Substituted Amphetamines (illustrated edition edition ed.). New York, NY: New York Academy of Sciences. 2000-02-01. ISBN 9781573312790. {{cite book}}: |edition= has extra text (help)
  39. ^ Jr, Donald G. Mcneil (2003-12-02). "Research On Ecstasy Is Clouded By Errors". The New York Times. ISSN 0362-4331. Retrieved 2015-10-12.
  40. ^ Massaro, Edward J. (2002-03-20). Handbook of Neurotoxicology. Springer Science & Business Media. ISBN 9781592591657.

---------------------------------

In a different context, "W-section" is a term commonly used by engineers and architects but most people won't understand us unless we say "I-beam".

Finally substituted amphetamines like substituted morphinans sounds like it belongs in a graduate level paper.

I appreciate the schematic drawings used in amphetamine and several other pages. Indeed they make those in medical texts look basic. I am concerned that many can't appreciate them, but are intimidated. Many don't understand the basics of neurotransmission at the presynaptic terminal. They can't pick out the basic actions from the detailed mechanisms.

Now I am not discounting the existing drawings, not proposing replacing or eliminating them. Rather drawings with reduced schematic detail might coexist with them. These may be sufficient for some readers, the limits of comprehending for some, a stepping stone for some making the detailed easier to grasp. Of course some will be baffled by the basic diagrams while they will be unnecessary for others. Maybe its analogous to a map US states or European countries, and one showing capital and major cities, lakes and rivers, major highways, time zones, and area/country codes.

What is missed is that such graphics present information overload. Most people don't understand the basic events of neurotransmission in the presynaptic terminal. Along with the more detailed, technical diagram, a more basic, less daunting diagram should exist. For some it will be a stepping stone for others sufficient or they most they can handle.

I wouldn't mind this term being mentioned but it is an esoteric term being forced on us.

There are too many sources to list where substituted amphetamines is used referring to MDMA type amphetamine analogues without reason for the author to define substituted amphetamines as excluding amphetamine itself. There are even more sources where the term amphetamines is used to described amphetamine and/or its derivatives without use of the term substituted amphetamines.

Regarding the graphic Pharmacodynamics of amphetamine enantiomers in a dopamine neuron

I suggest: Pharmacodynamics of amphetamine enantiomers in a dopamine neuron. Enantiomers is unnecessary since amphetamine is amphetamine enantiomers.

Could the colors be revised so amphetamine and amphetamine trafficking are both red.

At the risk of making this more detailed... Doesn't amphetamine also (reversibly) inhibit monoamine oxidase, reducing dopamine metabolism, thus increasing dopamine levels. (Enantiomer preferences of MAOA vs MAOB are schematically superfluous since both subtypes metabolize dopamine.)

1[1][2]

test outside[3][4]


Archive_53#Replacing_one_ambiguous_name_with_another

Wikipedia_talk:Article_titles/Archive_53#Replacing_one_ambiguous_name_with_another

Archive 53

Bob One[5]

Bob Two[6]


three[7]

KS Comp[8]

KS Pocket[9]

slide[10]

SA1[11]

sa2

sa3

Drink, Drugs and Dependence[12] sub as mdma[13]



2[14]

Drug Formula Molecular Mass Amphetamine Base Amphetamine
Base Content
Equipotent Dose
(g/mol) (percent) (30 mg dose) (assumed potency
of dextro:levo)
total base total dextro- levo- dextro- levo- 4x x
dextroamphetamine sulfate (C9H13N)2•H2SO4 368.49 270.41 73.38% 73.38%
22.0 mg
30.0
amphetamine sulfate (C9H13N)2•H2SO4 368.49 270.41 73.38% 36.69% 36.69%
11.0 mg
11.0 mg
48.0
30.0
Adderall 62.57% 47.49% 15.08%
14.2 mg
4.5 mg
42.9
35.2
25% dextroamphetamine sulfate (C9H13N)2•H2SO4 368.49 270.41 73.38% 73.38%
25% amphetamine sulfate (C9H13N)2•H2SO4 368.49 270.41 73.38% 36.69% 36.69%
25% dextroamphetamine saccharate (C9H13N)2•C6H10O8 480.55 270.41 56.27% 56.27%
25% amphetamine aspartate monohydrate (C9H13N)•C4H7NO4•H2O 286.32 135.21 47.22% 23.61% 23.61%
lisdexamfetamine dimesylate C15H25N3O•(CH4O3S)2 455.49 135.21 29.68% 29.68%
8.9mg
74.2
Notes
note 1. amphetamine base percent = molecular mass base / molecular mass total
note 2. equipotent dose = (1 / amphetamine base equivalent) * 22.015 = (molecular mass total / molecular mass base) * 22.015
note 3. 22.015 is constant scaling factor to make doses equivalent to 30 (units) dextroamphetamine sulfate.
note 4. any mass unit may be applied but scaled for typical mg dose range; rational for scaling factor.
note 5. potency of dextro to levo varies by effect; stimulant effects are dextro 4x of levo, clinical effects in some ADHD subtypes is equal.


Drug Molecular Mass Amphetamine Base Amphetamine
Base Content
Equipotent Dose
(g/mol) (percent) (30 mg dose) (potency of
dextro:levo)
total base total dextro- levo- dextro- levo- 4x x
dextroamphetamine sulfate 368.49 270.41 73.38% 73.38%
22.0 mg
30.0
amphetamine sulfate 368.49 270.41 73.38% 36.69% 36.69%
11.0 mg
11.0 mg
48.0
30.0
Adderall 62.57% 47.49% 15.08%
14.2 mg
4.5 mg
42.9
35.2
25% dextroamphetamine sulfate 368.49 270.41 73.38% 73.38%
25% amphetamine sulfate 368.49 270.41 73.38% 36.69% 36.69%
25% dextroamphetamine saccharate 480.55 270.41 56.27% 56.27%
25% amphetamine aspartate monohydrate 286.32 135.21 47.22% 23.61% 23.61%
lisdexamfetamine dimesylate 455.49 135.21 29.68% 29.68%
8.9mg
74.2
Notes
note 1. amphetamine base equivalent = molecular mass base / molecular mass total
note 2. equipotent dose = (1 / amphetamine base equivalent) * 22.015 = (molecular mass total / molecular mass base) * 22.015
note 3. 22.015 is constant scaling factor to make doses equivalent to 30 (units) dextroamphetamine sulfate.
note 4. any mass unit may be applied but scaled for typical mg dose range; rational for scaling factor.
note 5. potency of dextro to levo varies by effect; stimulant effects are dextro 4x of levo, clinical effects in some ADHD subtypes is equal.
The Big Boy Hamburger
Wian (original) Big Boy System (later) Frisch (Frisch's & Manners)
Wooden Big Boy pick

Dill pickle

Toasted top sesame seed bun Toasted top sesame seed bun Toasted top plain bun
Red relish (relish + chili sauce) Big Boy sauce (Thousand Island dressing)
1/8 lb beef patty 1/8 lb beef patty 1/8 lb beef patty
Mayonnaise Big Boy sauce (Thousand Island dressing) Shredded lettuce

Tartar sauce

Toasted center bun Toasted center bun Toasted center bun
Slice of American cheese
1/8 lb beef patty 1/8 lb beef patty 1/8 lb beef patty
Slice of American cheeseShredded lettuce

Mayonnaise

Slice of American cheeseShredded lettuce

Big Boy sauce (Thousand Island dressing)

Pickles
Toasted bottom bun Toasted bottom bun Toasted bottom bun

≈≈[15]

Equivalent doses (equivalent amounts of amphetamine base)[note 1]
30 mg dextroamphetamine sulfate 35 mg Adderall [note 2] 75 mg lisdexamfetamine dimesylate (Vyvanse)

123[16]


asdf[17]

•••®[18]

C2H5OH®[19]

C9H13O

C9H13O

C9H13O


amphetamine salt cation anion molecular weight % amphetamine
base
amphetamine base
mg in 10 mg
total amphetamine base dextro- levo-
25% Amphetamine Aspartate C9H13O C4H7NO4·H2O 286.32 135.21 47.2% 0.59 mg 0.59 mg
25% Dextroamphetamine Saccharate (C9H13O)2 C6H10O8 480.55 270.41 56.3% 1.41 mg
25% Dextroamphetamine Sulfate (C9H13O)2 H2SO4 368.49 270.41 73.4% 1.83 mg
25% Amphetamine Sulfate (C9H13O)2 H2SO4 368.49 270.41 73.4% 0.92 mg 0.92 mg
Total 62.6% 4.75 mg 1.51 mg

Comparison

100% Dextromphetamine Sulfate (C9H13O)2 H2SO4 368.49 270.41 73.4% 7.34 mg



Amphetamine base in marketed amphetamine medications
drug / drug component formula molecular weight amphetamine base amphetamine base
equivalence
approx.
equipotent dose
(g/mol) (percent) (30 mg dose)
total base total dextro- levo- dextro- levo-
dextroamphetamine sulfate (Dexedrine®)[20][21] (C9H13N)2•H2SO4
368.49
270.41
73.4%
73.4%
22.0 mg
30 mg
mixed amphetamine salts (Adderall®)
62.6%
47.5%
15.1%
14.2 mg
4.5 mg
35 mg
25% dextroamphetamine sulfate[20][21] (C9H13N)2•H2SO4
368.49
270.41
73.4%
73.4%
25% amphetamine sulfate[22] (C9H13N)2•H2SO4
368.49
270.41
73.4%
36.7%
36.7%
25% dextroamphetamine saccharate[23] (C9H13N)2•C6H10O8
450.55
270.41
56.3%
56.3%
25% amphetamine aspartate monohydrate[24] (C9H13N)•C4H7NO4•H2O
286.32
135.21
47.2%
23.6%
23.6%
lisdexamfetamine dimesylate (Vyvanse®)[25] C15H25N3O•(CH4O3S)2
455.49
135.21
29.7%
29.7%
8.9 mg
75 mg
Molecular weights were calculated using Lenntech (online) Molecular Weight Calculator[26] Mixed amphetamine salts base percentage = sum of component values / 4.

Approximate equivalency: 30 mg dextroamphetamine ≈ 35 mg Adderall ≈ 75 mg lisdexamfetamine (Vyvanse). (Assuming levoamphetamine and dextroamphetamine are equipotent.)

References

  1. ^ Feinberg, S. Shalom (2004-11-01). "Combining stimulants with monoamine oxidase inhibitors: a review of uses and one possible additional indication". The Journal of Clinical Psychiatry. 65 (11): 1520–1524. ISSN 0160-6689. PMID 15554766.
  2. ^ Stewart, Jonathan W.; Deliyannides, Deborah A.; McGrath, Patrick J. (2014-01-01). "How treatable is refractory depression?". Journal of Affective Disorders. 167: 148–152. doi:10.1016/j.jad.2014.05.047. ISSN 1573-2517. PMID 24972362.
  3. ^ Green-Hernandez, Carol; Singleton, Joanne K.; Aronzon, Daniel Z. (2001-01-01). Primary Care Pediatrics. Lippincott Williams & Wilkins. p. 243. ISBN 9780781720083.
  4. ^ "Dexedrine, ProCentra(dextroamphetamine) dosing, indications, interactions, adverse effects, and more". reference.medscape.com. Retrieved 2015-10-04. Onset of action: 1-1.5 hr
  5. ^ Wells, Douglas G.; Bjorksten, Andrew R. (1989-01-01). "monoamine oxidase inhibitors revisited". Canadian Journal of Anaesthesia. 36 (1): 64–74. doi:10.1007/BF03010890. ISSN 0832-610X.
  6. ^ Mantle, T. J.; Tipton, K. F.; Garrett, N. J. (1976-09-15). "Inhibition of monoamine oxidase by amphetamine and related compounds". Biochemical Pharmacology. 25 (18): 2073–2077. ISSN 0006-2952. PMID 985546.
  7. ^ Wallace, Lane J. (2012-07-01). "Effects of amphetamine on subcellular distribution of dopamine and DOPAC". Synapse (New York, N.Y.). 66 (7): 592–607. doi:10.1002/syn.21546. ISSN 1098-2396. PMID 22314940.
  8. ^ Sadock, Benjamin J.; Sadock, Virginia A.; Ruiz, Pedro, eds. (2009). "11.Substance-Related Disorders". Kaplan & Sadock's comprehensive textbook of psychiatry. Vol. 1 (9th ed.). Lippincott Williams & Wilkins. p. 1260. ISBN 0781768993. With a few notable exceptions, animals in experimental situations self-administer most of the drugs that humans tend to use and abuse. Included among the drugs are μ- and δ-opioid agonists, cocaine, amphetamine and amphetamine-like agents, substituted amphetamines, such as MDMA, alcohol, barbiturates, many benzodiazepines, a number of volatile gases and vapors (e.g., nitrous oxide and ether), PCP, and nicotine.
  9. ^ Kaplan and Sadock's Pocket Handbook of Clinical Psychiatry, 5th Edition (Fifth edition ed.). Philadelphia, Pa.: Lippincott Williams and Wilkins. 2010-04-01. p. 135. ISBN 9781605472645. The classic substituted amphetamines include MDMA, MDEA, 2,5-dimethoxy-4-methylamphetamine (DOM, STP), dimethyltryptamine (DMT), MMDA, and trimethoxyamphetamine (TMA), which are also commonly classified with amphetamines. {{cite book}}: |edition= has extra text (help)
  10. ^ "Substituted Amphetamines". research.chem.psu.edu. Retrieved 2015-10-07.
  11. ^ O’Callaghan, James P. (2002). "Neurotoxic effects of substituted amphetamines in rats and mice.". Handbook of Neurotoxicology. Humana Press.
  12. ^ Rattray, Marcus (2002-05-31). "Chapter 12. Ecstasy". In Caan, Woody; de Belleroche, Jackie (eds.). Drink, Drugs and Dependence: From Science to Clinical Practice (1st edition ed.). London: Routledge. p. 132. ISBN 9780415278911. MDMA is one of a number of closely related substances known as substituted amphetamines.... The substituted amphetamines are entirely synthetic ... in most western countries substituted amphetamines are illegal... Some ecstasy tablets many not contain any substituted amphetamines at all, they may contain methamphetamnine, LSD, ketamine or inert substances. {{cite book}}: |edition= has extra text (help)
  13. ^ Caan, Woody; Belleroche, Jackie de (2003-09-02). Drink, Drugs and Dependence: From Science to Clinical Practice. Routledge. ISBN 9781134468270.
  14. ^ Kessler, S. (1996-01-01). "Drug therapy in attention-deficit hyperactivity disorder". Southern Medical Journal. 89 (1): 33–38. ISSN 0038-4348. PMID 8545689.
  15. ^ "Dexedrine [monograph]" (PDF). United States Food and Drug Administration. Amedra Pharmaceuticals LLC. October, 2013. Retrieved September 6, 2015. {{cite web}}: Check date values in: |date= (help)
  16. ^ Kolar, Dusan; Keller, Amanda; Golfinopoulos, Maria; Cumyn, Lucy; Syer, Cassidy; Hechtman, Lily (2008-04-01). "Treatment of adults with attention-deficit/hyperactivity disorder". Neuropsychiatric Disease and Treatment. 4 (2): 389–403. ISSN 1176-6328. PMC 2518387. PMID 18728745.
  17. ^ Rattray, Marcus (2003). "12. Ecstasy". In Caan, Woody (ed.). Drink, Drugs and Dependence: From Science to Clinical Practice. Routledge. p. 133.
  18. ^ Lees, Andrew. "The Story of "Speed" from "Cloud Nine" to Brain Gain". PubMed. Retrieved August 18, 2015.
  19. ^ O'Brien, BA (May 1982). "Differentiation of amphetamine and its major hallucinogenic derivatives using thin-layer chromatography" (PDF). Journal of Anylitical Toxicology. 6 (3): 146. PMID 7109558. Retrieved August 18, 2015. Figure 1. Structures of amphetamine and the major substituted derivatives
  20. ^ a b Mallinckrodt Product Specifications: Dextroamphetamine Sulfate USP (pdf), March 2014, retrieved August 19, 2015
  21. ^ a b Tocris: D-amphetamine sulfate, 2015, retrieved August 19, 2015
  22. ^ Mallinckrodt Product Specifications: Amphetamine Sulfate USP (pdf), March 2014, retrieved August 19, 2015
  23. ^ Mallinckrodt Product Specifications: Dextroamphetamine Saccharate (pdf), March 2014, retrieved August 19, 2015
  24. ^ Mallinckrodt Product Specifications: Amphetamine Aspartate (pdf), March 2014, retrieved August 19, 2015
  25. ^ label/2007/021977lbl.pdf Vyvanse (lisdexamfetamine dimesylate) [monograph] (pdf), 2007, retrieved August 19, 2015 {{citation}}: Check |url= value (help)
  26. ^ Lenntech Molecular Weight Calculator, retrieved August 19, 2015

test[1]


The following issues should be addressed. Comments please.

In the Lead section:

  1. Revise: "...in the United States, where both racemic methamphetamine and dextromethamphetamine are classified as schedule II controlled substances. In contrast, enantiopure levomethamphetamine is an over-the-counter drug which is marketed as a nasal decongestant in the United States." Sounds like isolated levomethamphetamine is not a controlled substance in the U.S. Very wrong. "Under 21 C.F.R. § 1308.12(d), methamphetamine or its isomers is a Schedule II controlled substance unless specially excepted."[2][3] Two exceptions exist for nasal inhalers made by Vicks and Classic Pharmaceuticals (now Aphena, who packages the product for others such as CVS and RiteAid).[4] Every other form or quantity of levomethamphetamine, even isolating it from the inactive ingredients in these inhalers makes it a Schedule II drug.[5] Could be revised to: "...in the United States, where all forms of methamphetamine are classified as schedule II controlled substances. However, decongestant nasal inhalers containing limited quantities of levoamphetamine are permitted as over-the-counter products in the United States." but a more comprehensive revision would be better. There is really no need to mention nasal inhalers in the lead since it is addressed in the Medical section of the article.

In the Medical section:

  1. "Severe" should be deleted. "[M]ethamphetamine ... has been approved by the FDA for treating severe ADHD" Severe ADHD does not appear in the FDA monograph.[6] Compared to other stimulants methamphetamine is rarely prescribed for many reasons: because of its profound illicit use and greater concerns of abuse, greater number/promotion of other stimulants/formulations, neurotoxic potential, high cost/exclusions from insurance formularies, extremely limited supply due to stingy/declining DEA issued Production Quotas[7], and lack of practitioner experience / lack of current therapeutic research / exclusion from medical reference guides. When used, methamphetamine is likely tried in persons with ADHD whose symptoms are not relieved by other ADHD medications. Some may be persons with severe ADHD but some might simply be persons with treatment resistant ADHD. Nonetheless the FDA indications do not specify severe ADHD. (Don't confuse American Society of Health-System Pharmacists' monographs with FDA monographs.)[8]
  2. Wrong definition for exogenous obesity. "... and [for treating] exogenous obesity (obesity originating from factors outside the patient's control)" The phrase in parenthesis should be deleted (or corrected) because it is not the definition of exogenous obesity but is true for endogenous obesity. Exogenous obesity means consuming more calories than needed or used by the body[9] (as compared to endogenous obesity which means obesity resulting from endocrine or metabolic dysfunction).[10] For example, obesity may result from hypothyroidism and hypothyroidism is outside the patient's control but this would not be considered exogenous obesity.
  3. I challenge this statement: "It is rarely prescribed due to concerns over toxicity." Accepting that A. methamphetamine is neurotoxic and B. methamphetamine is rarely prescribed does not prove the assertion. It is more likely that its recreational reputation (including violence and personal devastation) and the availability of other efficacious drugs (stimulants & non-stimulants) is the most prominent reason. Measures which were established to combat abuse/diversion such as the Controlled Substances Act, Prescription Monitoring Programs and state/DEA disciplinary actions against prescribers clearly are a major influence on methamphetamine prescribing. It would be a much better to say, "It is rarely prescribed due to concerns over abuse and toxicity." or similar. ("Recreational use" is the MOS preferred term to abuse.) Otherwise please provide support for the prescription-toxicity assertion, not just A and B above. (Granted it isn't easy to find specific quality evidence about this.)
  4. Change "sometimes" to "also". "... methamphetamine is sometimes prescribed off label for narcolepsy and idiopathic hypersomnia." "Also" would be more appropriate than "sometimes". "Sometimes" infers methamphetamine is a fringe therapy while the the drug has a long established history treating narcolepsy and the medical community considers narcolepsy a valid indication.
  5. The FDA black box warning should be deleted. The FDA requires a number of drugs to display black box warnings but I am aware of no others where it is copied verbatim into a Wikipedia article. It should be sufficient to mention the existence of the black box warning, cite the source and if needed, put the actual quoted warning in a footnote. The concerns raised in the warning should already exist elsewhere in the article.
  6. Consider neuroprotective effects. While the article repeatedly mentions neurotoxicity, editors might consider methamphetamine's neuroprotective effects at low doses in persons with stroke and CNS trauma.[11]

References

  1. ^ Hutson, Peter H.; Pennick, Michael; Secker, Roger (2014-12-01). "Preclinical pharmacokinetics, pharmacology and toxicology of lisdexamfetamine: a novel d-amphetamine pro-drug". Neuropharmacology. 87: 41–50. doi:10.1016/j.neuropharm.2014.02.014. ISSN 1873-7064. PMID 24594478.
  2. ^ "949 F2d 1065 United States v. R Youngblood | OpenJurist". openjurist.org. Retrieved 2015-09-01.
  3. ^ "Title 21 CFR - PART 1308 - Section 1308.12 Schedule II". www.deadiversion.usdoj.gov. Retrieved 2015-09-01.
  4. ^ "Title 21 CFR - PART 1308 - Section 1308.22 Excluded substances". www.deadiversion.usdoj.gov. Retrieved 2015-09-01.
  5. ^ "FindLaw's Supreme Court of Mississippi case and opinions". Findlaw. Retrieved 2015-09-01.
  6. ^ "DESOXYN® Methamphetamine Hydrochloride Tablets, USP [Monograph]" (PDF). U. S. Food and Drug Administration. Retrieved September 1, 2015.
  7. ^ "Government Report Slams DEA for Oversight of Drug Production Quota System | RAPS". www.raps.org. Retrieved 2015-09-01.
  8. ^ "Methamphetamine Hydrochloride Monograph for Professionals - Drugs.com". www.drugs.com. Retrieved 2015-09-01.
  9. ^ "exogenous obesity". Retrieved 2015-09-01.
  10. ^ "endogenous obesity". Retrieved 2015-09-01.
  11. ^ Rau, Thomas; Ziemniak, John; Poulsen, David (2015-02-25). "The neuroprotective potential of low-dose methamphetamine in preclinical models of stroke and traumatic brain injury". Progress in Neuro-Psychopharmacology & Biological Psychiatry. doi:10.1016/j.pnpbp.2015.02.013. ISSN 1878-4216. PMID 25724762.


Cite error: There are <ref group=note> tags on this page, but the references will not show without a {{reflist|group=note}} template (see the help page).