Aminorex: Difference between revisions

{{Short description|Chemical compound}}

{{cs1 config|name-list-style=vanc|display-authors=6}}

| verifiedrevid = 447552025

| IUPAC_name = (''RS'')-5-Phenyl-4,5-dihydro-1,3-oxazol-2-amine

| image = Aminorex structure.svg

| alt = Skeletal formula

| image2 = Aminorex molecule ball.png

| alt2 = Ball-and-stick model of aminorex

| chirality = [[Racemic mixture]]

| legal_BR = B2

| legal_BR_comment = <ref>{{cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-03-31 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=2023-08-03 |access-date=2023-08-16 |publisher=[[Diário Oficial da União]] |language=pt-BR |publication-date=2023-04-04}}</ref>

| legal_UK = Class C

| legal_DE = Anlage II

| routes_of_administration =

| excretion =

| CAS_number_Ref = {{cascite|correct|??}}

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| UNII_Ref = {{fdacite|correct|FDA}}

| smiles = NC1=NCC(C2=CC=CC=C2)O1

'''Aminorex''' ('''Menocil''', '''Apiquel''', '''aminoxaphen''', '''aminoxafen''', '''McN-742''') is a weight loss ([[anorectic]]) [[stimulant]] [[drug]]. It was withdrawn from the market after it was found to cause [[pulmonary hypertension]].<ref name="pmid11083709">{{cite journal | vauthors = Gaine SP, Rubin LJ, Kmetzo JJ, Palevsky HI, Traill TA | title = Recreational use of aminorex and pulmonary hypertension | journal = Chest | volume = 118 | issue = 5 | pages = 1496–1497 | date = November 2000 | pmid = 11083709 | doi = 10.1378/chest.118.5.1496 | url = http://www.chestjournal.org/cgi/pmidlookup?view=long&pmid=11083709 | url-status = dead | archive-url = https://archive.today/20130112175859/http://www.chestjournal.org/cgi/pmidlookup?view=long&pmid=11083709 | archive-date = 2013-01-12 }}</ref> In the U.S., it is an illegal [[Controlled Substances Act#Schedule I controlled substances|Schedule I]] drug, meaning it has high abuse potential, no accepted medical use, and a poor safety profile.

Aminorex, in the 2-amino-5-aryl oxazoline class, was developed by [[McNeil Laboratories]] in 1962.<ref>{{cite patent | country = US | number = 3161650 | url = https://patents.google.com/patent/US3161650A | inventor = Ireland PG | assign = Janssen Pharmaceuticals Inc. | gdate = 15 December 1964 | title = 2-Amino-5-Aryloxazoline Products}}</ref> It is closely related to [[4-methylaminorex]]. Aminorex has been shown to have locomotor stimulant effects, lying midway between [[dextroamphetamine]] and [[methamphetamine]]. Aminorex effects have been attributed to the release of [[catecholamines]].<ref name="pmid9884392">{{cite journal | vauthors = Fishman AP | title = Aminorex to fen/phen: an epidemic foretold | journal = Circulation | volume = 99 | issue = 1 | pages = 156–161 | date = Jan 1991 | pmid = 9884392 | doi = 10.1161/01.CIR.99.1.156 | doi-access = free }}</ref> It can be produced as a [[metabolite]] of the worming medication [[levamisole]], which is sometimes used as a [[cutting agent]] of illicitly produced [[cocaine]].<ref>{{cite journal | vauthors = Ho EN, Leung DK, Leung GN, Wan TS, Wong AS, Wong CH, Soma LR, Rudy JA, Uboh C, Sams R | title = Aminorex and rexamino as metabolites of levamisole in the horse | journal = Analytica Chimica Acta | volume = 638 | issue = 1 | pages = 58–68 | date = April 2009 | pmid = 19298880 | doi = 10.1016/j.aca.2009.02.033 | bibcode = 2009AcAC..638...58H }}</ref><ref name="pmid21531521">{{cite journal | vauthors = Bertol E, Mari F, Milia MG, Politi L, Furlanetto S, Karch SB | title = Determination of aminorex in human urine samples by GC-MS after use of levamisole | journal = Journal of Pharmaceutical and Biomedical Analysis | volume = 55 | issue = 5 | pages = 1186–1189 | date = July 2011 | pmid = 21531521 | doi = 10.1016/j.jpba.2011.03.039 }}</ref>

== Pharmacology ==

Aminorex has been found to act as a reuptake inhibitor at the dopamine and norepinephrine transporters, with releasing agent properties at the serotonin transporter.<ref>{{cite journal | vauthors = Hofmaier T, Luf A, Seddik A, Stockner T, Holy M, Freissmuth M, Ecker GF, Schmid R, Sitte HH, Kudlacek O | title = Aminorex, a metabolite of the cocaine adulterant levamisole, exerts amphetamine like actions at monoamine transporters | journal = Neurochemistry International | volume = 73 | issue = 100 | pages = 32–41 | date = July 2014 | pmid = 24296074 | pmc = 4077236 | doi = 10.1016/j.neuint.2013.11.010 }}</ref>

It was discovered in 1962 by [[Edward John Hurlburt]],<ref>{{cite patent| country = US | number = 3115494 | title = 2-amino-5, 6-dihydro-4ii-1, 3-oxazines and a process for their preparation | inventor = Albert MG, Ireland PG | assign = Janssen Pharmaceuticals Inc. | gdate = 2 December 1963 | url = https://www.google.com/patents/US3115494}}</ref> and was quickly found in 1963 to have an [[anorectic]] effect in [[rat]]s. It was introduced as a [[Prescription drug|prescription]] appetite suppressant in [[Germany]], [[Switzerland]] and [[Austria]] in 1965, but was withdrawn in 1972 after it was found to cause [[pulmonary hypertension]] in approximately 0.2% of patients, and was linked to a number of deaths.<ref name="pmid9884392"/><ref>{{cite journal | vauthors = Weigle DS | title = Pharmacological therapy of obesity: past, present, and future | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 88 | issue = 6 | pages = 2462–2469 | date = June 2003 | pmid = 12788841 | doi = 10.1210/jc.2003-030151 | doi-access = free }}</ref>

The synthesis was first reported in a [[structure-activity relationship]] study of 2-amino-5-aryl-2-oxazolines, where aminorex was found to be approximately 2.5 times more potent than ''D''-amphetamine sulfate in inducing anorexia in rats, and was also reported to have CNS stimulant effects.

[[Image:Aminorex rxn mech.png|700px|center|thumb]]

The [[racemic]] synthesis involves addition/cyclization reaction of 2-amino-1-phenylethanol with [[cyanogen bromide]].<ref name="pmid14185981">{{cite journal | vauthors = Poos GI, Carson JR, Rosenau JD, Roszkowski AP, Kelley NM, Mcgowin J | title = 2-Amino-5-aryl-2-oxazolines. Potent New Anorectic Agents. | journal = Journal of Medicinal Chemistry | volume = 6 | issue = 3 | pages = 266–272 | date = May 1963 | pmid = 14185981 | doi = 10.1021/jm00339a011 }}</ref> A similar synthesis has been also published.<ref name="pmid14698148">{{cite journal | vauthors = Ueda S, Terauchi H, Yano A, Ido M, Matsumoto M, Kawasaki M | title = 4,5-Disubstituted-1,3-oxazolidin-2-imine derivatives: a new class of orally bioavailable nitric oxide synthase inhibitor | journal = Bioorganic & Medicinal Chemistry Letters | volume = 14 | issue = 2 | pages = 313–316 | date = January 2004 | pmid = 14698148 | doi = 10.1016/j.bmcl.2003.11.010 }}</ref> In a search for a cheaper synthetic route, a German team developed an alternative route<ref>{{cite patent | country = DE | number = 2101424 | title = 2-Amino-5-phenyl-2-oxazoline preparation | inventor = | url = https://patents.google.com/patent/DE2101424A1 | assign = Polska Akademia Nauk Instytut Chemn Organicznej, Warschau }}</ref> which, by using chiral styrene oxide, allows an enantiopure product.

* [[List of aminorex analogues]]

== References ==

{{Reflist|2}}

{{Anorectics}}

{{Monoamine releasing agents}}

[[Category:5-HT2B agonists]]

[[Category:Norepinephrine-dopamine releasing agents]]

[[Category:Aminorexes]]