Substituted amphetamine

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A variety of prodrugs of amphetamine and/or methamphetamine exist, and include amfecloral, amfetaminil, benzphetamine, clobenzorex, D-deprenyl, deprenyl, dimethylamphetamine, ethylamphetamine, fencamine, fenethylline, fenproporex, furfenorex, lisdexamfetamine, mefenorex, prenylamine, and selegiline.{{cite book|author1=Reinhard Dettmeyer|author2=Marcel A. Verhoff|author3=Harald F. Schütz|title=Forensic Medicine: Fundamentals and Perspectives|url=https://books.google.com/books?id=yHHABAAAQBAJ&pg=PA519|date=9 October 2013|publisher=Springer Science & Business Media|isbn=978-3-642-38818-7|pages=519–}}

{{See also|List of Russian drugs}}

A number of synthetic Russian amphetamine derivatives have been developed, including alafen (amphetamine–β-alanine), feprosidnine, gamofen (amphetamine–GABA), mesocarb, methylphenatine, pabofen (amphetamine–PABA), phenatine (amphetamine–niacin; N-nicotinoylamphetamine), phenylphenamine (phenylamphetamine), propylphenamine (propylamphetamine), pyridoxiphen (amphetamine–pyridoxine), and thiophenatine (N-thionicotinoylamphetamine).

{{Expand section|with=substituents and structures for phenelzine, phenylephrine, phenylpropanolamine, selegiline, fenfluramine, mescaline, diethylpropion, desmethylselegiline, and benzphetamine from [https://books.google.com/books?id=9JLiJcjdqkcC&pg=PA5 this table].|date=February 2019|small=no}}

File:Phenylethyl Amine General Formula V1.svg in blue with its substitution points marked. Amphetamine and its substituted derivatives contain a CH₃ group at the alpha-position (R^α).]]

File:Amphetamine numbered.svg which is unmarked. The wavy line between α carbon and CH₃ group indicates isomerism; the CH₃ group may either be towards or away from the viewer.]]

Amphetamines are a subgroup of the substituted phenethylamine class of compounds. Substitution of hydrogen atoms results in a large class of compounds. Typical reaction is substitution by methyl and sometimes ethyl groups at the amine and phenyl sites:Goldfrank, pp. 1125–1127Glennon, pp. 184–187Schatzberg, p.843

{{Main|History and culture of substituted amphetamines}}

Ephedra was used 5000 years ago in China as a medicinal plant; its active ingredients are alkaloids ephedrine, pseudoephedrine, norephedrine (phenylpropanolamine) and norpseudoephedrine (cathine). Natives of Yemen and Ethiopia have a long tradition of chewing khat leaves to achieve a stimulating effect. The active substances of khat are cathinone and, to a lesser extent, cathine.{{cite book|author = Paul M Dewick|title = Medicinal Natural Products. A Biosynthetic Approach. Second Edition|url = https://books.google.com/books?id=A4zptjOJfKQC&pg=PP1|year = 2002|publisher = Wiley|isbn = 978-0-471-49640-3|pages =383–384}}

Amphetamine was first synthesized in 1887 by Romanian chemist Lazăr Edeleanu, although its pharmacological effects remained unknown until the 1930s.Snow, p. 1 MDMA was produced in 1912 (in 1914, according to other sources{{cite journal|author = A. Richard Green|doi=10.1124/pr.55.3.3|title = The Pharmacology and Clinical Pharmacology of 3,4-Methylenedioxymethamphetamine (MDMA, Ecstasy)|pmid = 12869661|year = 2003|journal = Pharmacological Reviews|volume = 55|issue = 3|pages = 463–508|name-list-style=vanc|display-authors = 1|last2 = Mechan|first2 = AO|last3 = Elliott|first3 = JM|last4 = O'Shea|first4 = E|last5 = Colado|first5 = MI|s2cid=1786307}}) as an intermediate product. However, this synthesis also went largely unnoticed.Goldfrank, p. 1125 In the 1920s, both methamphetamine and the dextrorotatory optical isomer of amphetamine, dextroamphetamine, were synthesized. This synthesis was a by-product of a search for ephedrine, a bronchodilator used to treat asthma extracted exclusively from natural sources. Over-the-counter use of substituted amphetamines was initiated in the early 1930s by the pharmaceutical company Smith, Kline & French (now part of GlaxoSmithKline), as a medicine (Benzedrine) for colds and nasal congestion. Subsequently, amphetamine was used in the treatment of narcolepsy, obesity, hay fever, orthostatic hypotension, epilepsy, Parkinson's disease, alcoholism and migraine.Goldfrank, p. 1119 The "reinforcing" effects of substituted amphetamines were quickly discovered, and the misuse of substituted amphetamines had been noted as far back as 1936.

File:Amph salts.jpg

During World War II, amphetamines were used by the German military to keep their tank crews awake for long periods, and treat depression. It was noticed that extended rest was required after such artificially induced activity. The widespread use of substituted amphetamines began in postwar Japan and quickly spread to other countries. Modified "designer amphetamines", such as MDA and PMA, have gained in popularity since the 1960s. In 1970, the United States adopted "the Controlled Substances Act" that limited non-medical use of substituted amphetamines. Street use of PMA was noted in 1972.{{cite journal|author = Liang Han Ling|title = Poisoning with the recreational drug paramethoxyamphetamine ("death" )|url = http://www.mja.com.au/public/issues/174_09_070501/ling/ling.html|journal = The Medical Journal of Australia|year = 2001|volume = 174|pages = 453–5|pmid = 11386590|issue = 9|name-list-style = vanc|display-authors = 1|last2 = Marchant|first2 = C|last3 = Buckley|first3 = NA|last4 = Prior|first4 = M|last5 = Irvine|first5 = RJ|doi = 10.5694/j.1326-5377.2001.tb143372.x|url-status = live|archive-url = https://web.archive.org/web/20091126043611/http://www.mja.com.au/public/issues/174_09_070501/ling/ling.html|archive-date = 26 November 2009|df = dmy-all|hdl = 2440/14508|s2cid = 37596142|hdl-access = free}} MDMA emerged as a substitute for MDA in the early 1970s.{{cite news|last1=Foderaro|first1=Lisa W.|title=Psychedelic Drug Called Ecstasy Gains Popularity in Manhattan Nightclubs|url=https://www.nytimes.com/1988/12/11/nyregion/psychedelic-drug-called-ecstasy-gains-popularity-in-manhattan-nightclubs.html?pagewanted=2|access-date=27 August 2015|work=The New York Times|date=11 December 1988|url-status=live|archive-url=https://web.archive.org/web/20151117042408/http://www.nytimes.com/1988/12/11/nyregion/psychedelic-drug-called-ecstasy-gains-popularity-in-manhattan-nightclubs.html?pagewanted=2|archive-date=17 November 2015|df=dmy-all}} American chemist Alexander Shulgin first synthesized the drug in 1976 and through him the drug was briefly introduced into psychotherapy.{{cite journal|last1=Benzenhöfer|first1=Udo|last2=Passie|first2=Torsten|title=Rediscovering MDMA (ecstasy): the role of the American chemist Alexander T. Shulgin|journal=Addiction|date=9 July 2010|volume=105|issue=8|pages=1355–1361|doi=10.1111/j.1360-0443.2010.02948.x|pmid=20653618}} Recreational use grew and in 1985 MDMA was banned by the US authorities in an emergency scheduling initiated by the Drug Enforcement Administration.Snow, p. 71

Since the mid-1990s, MDMA has become a popular entactogenic drug among the youth and quite often non-MDMA substances were sold as ecstasy.Goldfrank, p. 1121 Ongoing trials are investigating its efficacy as an adjunct to psychotherapy in the management of treatment-resistant post-traumatic stress disorder (PTSD).{{cite journal|author = Mithoefer M.|title = The safety and efficacy of ±3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study|journal = Journal of Psychopharmacology|year = 2011|volume=25|pages=439–52 |doi=10.1177/0269881110378371|name-list-style=vanc|display-authors = 1|last2 = Wagner|first2 = M. T.|last3 = Mithoefer|first3 = A. T.|last4 = Jerome|first4 = L.|last5 = Doblin|first5 = R.|issue = 4|pmid = 20643699|pmc = 3122379}}

• Substituted phenethylamines
• Substituted β-hydroxyamphetamines
• Substituted methylenedioxyphenethylamines
• Substituted cathinones
• Substituted phenylmorpholines
• Substituted methoxyphenethylamine
• 2Cs, DOx, 4Cs, 25-NB, 3C, substituted mescaline analogue, FLY
• Substituted tryptamines
• Substituted α-alkyltryptamines
• PiHKAL
• The Shulgin Index

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• {{cite book|author = Ghodse, Hamid|title = Drugs and Addictive Behaviour. A Guide to Treatment. 3rd Edition|url = https://books.google.com/books?id=3WF79shLxB4C&pg=PP1|year = 2002|publisher = Cambridge University Press|pages = 501|isbn = 978-0-511-05844-8}}
• {{cite book|author = Glennon, Richard A.|title = The American Psychiatric Publishing textbook of substance abuse treatment|chapter = Neurobiology of Hallucinogens|chapter-url = https://books.google.com/books?id=6wdJgejlQzYC&pg=PA181|year = 2008|publisher = American Psychiatric Publishing|isbn = 978-1-58562-276-4}}
• {{cite book|author1 = Goldfrank, Lewis R.|author2 = Flomenbaum, Neal|name-list-style = amp|title = Goldfrank's Toxicologic Emergencies, 8th Edition|url = https://books.google.com/books?id=cvJuLqBxGUcC&pg=PP1|year = 2006|publisher = McGraw Hill|isbn = 978-0-07-147914-1}}
• {{cite book|author = Katzung, Bertram G.|title = Basic & clinical pharmacology. 11th edition|url = https://books.google.com/books?id=srRLpM5miGYC&pg=PP1|year = 2009|publisher = McGraw-Hill Medical|isbn = 978-0-07-160405-5}}{{Dead link|date=March 2024 |bot=InternetArchiveBot |fix-attempted=yes }}
• {{cite book|author = Ledgard, Jared |title = A Laboratory History of Narcotics. Volume 1. Amphetamines and Derivatives|year = 2007|publisher = Jared Ledgard|pages = 268|isbn = 978-0-615-15694-1}}
• {{cite book|author1 = Schatzberg, Alan F.|author2 = Nemeroff, Charles B.|name-list-style = amp|title = The American Psychiatric Publishing Textbook of Psychopharmacology|url = https://books.google.com/books?id=Xx7iNGdV25IC&pg=PP1|year = 2009|publisher = The American Psychiatric Publishing|isbn = 978-1-58562-309-9}}
• {{cite book|author =Snow, Otto |title = Amphetamine syntheses|year = 2002|publisher = Thoth Press|isbn = 978-0-9663128-3-6}}
• {{cite book|vauthors=Veselovskaya NV, Kovalenko AE |title = Drugs. Properties, effects, pharmacokinetics, metabolism|year = 2000|location = MA|publisher = Triada-X|isbn = 978-5-94497-029-9}}

{{Refend}}

• {{Commons category-inline|Amphetamines}}

{{Amphetamine|state=expanded}}

{{Chemical classes of psychoactive drugs}}

{{Monoamine releasing agents}}

{{Serotonin receptor modulators}}

{{Phenethylamines}}

{{Authority control}}

{{DEFAULTSORT:Substituted Amphetamine}}

Category:Amphetamine

Category:Chemical classes of psychoactive drugs