Etilamfetamine

{{Short description|Chemical compound}} {{Drugbox | verifiedrevid = 415324453 | drug_name = Ethylamphetamine | INN = Etilamfetamine | IUPAC_name = ''N''-Ethyl-1-phenyl-propan-2-amine | image = Ethylamphetamine structure.svg | width = 225px | image_class = skin-invert-image | image2 = Etilamfetamine molecule ball.png | image_class2 = bg-transparent | width2 = 250px | alt2 = Ball-and-stick model of etilamfetamine molecule

| tradename = Apetinil; Adiparthrol | pregnancy_category = | legal_BR = B1 | 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_CA = Schedule I | legal_US = Schedule I | legal_DE = Anlage II | legal_UK = Class C | routes_of_administration = Oral, sublingual, insufflated, inhaled (vaporized), intravenous, rectal

| bioavailability = | protein_bound = | metabolism = Hepatic (''N''-dealkylation, others)<ref name="BeckettShenoy1973" /> | metabolites = Amphetamine<ref name="BeckettShenoy1973" /> | elimination_half-life = | excretion = Urine (5–18% as amphetamine)<ref name="BeckettShenoy1973" />

| CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 457-87-4 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 022YON1XMX | ATC_prefix = A08 | ATC_suffix = AA06 | PubChem = 9982 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 9588 | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D07114 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 276443 | synonyms = Etilamfetamine; Ethylamphetamine; ''N''-Ethylamphetamine; PAL-99; PAL99

| C=11 | H=17 | N=1 | SMILES = N(C(Cc1ccccc1)C)CC | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C11H17N/c1-3-12-10(2)9-11-7-5-4-6-8-11/h4-8,10,12H,3,9H2,1-2H3 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = YAGBSNMZQKEFCO-UHFFFAOYSA-N }}

'''Etilamfetamine''', also known as '''''N''-ethylamphetamine''' and formerly sold under the brand names '''Apetinil''' and '''Adiparthrol''', is a stimulant drug of the amphetamine family. It was invented in the early 20th century and was subsequently used as an anorectic or appetite suppressant in the 1950s,<ref>{{cite journal | vauthors = Junet R | title = L'éthylamphétamine dans le traitement de l'obésité | trans-title = Ethylamphetamine in the treatment of obesity | journal = Praxis | volume = 45 | issue = 43 | pages = 986–988 | date = October 1956 | pmid = 13389142 }}</ref> but was not as commonly used as other amphetamines such as amphetamine, methamphetamine, and benzphetamine, and was largely discontinued once newer drugs such as phenmetrazine were introduced.

== Pharmacology == === Pharmacodynamics === ==== Monoamine releasing agent ==== Ethylamphetamine is a potent dopamine releasing agent (DRA) ''in vitro'', with an {{Abbrlink|EC50|half-maximal effective concentration}} of 88.5{{nbsp}}nM.<ref name="ReithBloughHong2015">{{cite journal | vauthors = Reith ME, Blough BE, Hong WC, Jones KT, Schmitt KC, Baumann MH, Partilla JS, Rothman RB, Katz JL | title = Behavioral, biological, and chemical perspectives on atypical agents targeting the dopamine transporter | journal = Drug Alcohol Depend | volume = 147 | issue = | pages = 1–19 | date = February 2015 | pmid = 25548026 | doi = 10.1016/j.drugalcdep.2014.12.005 | url = | pmc = 4297708 }}</ref> This is about 10-fold lower than the {{Abbr|EC50|half-maximal effective concentration}} of dextroamphetamine.<ref name="ReithBloughHong2015" /> The {{Abbr|EC50|half-maximal effective concentration}} values of ethylamphetamine for induction of norepinephrine and serotonin release were not reported.<ref name="ReithBloughHong2015" /> However, the {{Abbr|EC50|half-maximal effective concentration}} values of its dextrorotatory enantiomer dextroethylamphetamine have been reported and were 44.1{{nbsp}}nM, 28.8{{nbsp}}nM, and 333{{nbsp}}nM for norepinephrine, dopamine, and serotonin, respectively.<ref name="FitzgeraldGannonWalther2024">{{cite journal | vauthors = Fitzgerald LR, Gannon BM, Walther D, Landavazo A, Hiranita T, Blough BE, Baumann MH, Fantegrossi WE | title = Structure-activity relationships for locomotor stimulant effects and monoamine transporter interactions of substituted amphetamines and cathinones | journal = Neuropharmacology | volume = 245 | issue = | article-number = 109827 | date = March 2024 | pmid = 38154512 | doi = 10.1016/j.neuropharm.2023.109827 | pmc = 10842458 | url = }}</ref><ref name="Nicole2022">{{cite web | last=Nicole | first=Lauren | title=In vivo Structure-Activity Relationships of Substituted Amphetamines and Substituted Cathinones | date=2022 | website=ProQuest | url=https://www.proquest.com/openview/a207e98868b4a9c5ac9296fb24abbcd8/ | access-date=5 December 2024 | quote = FIGURE 2-6: Release: Effects of the specified test drug on monoamine release by DAT (red circles), NET (blue squares), and SERT (black traingles) in rat brain tissue. [...] EC50 values determined for the drug indicated within the panel. [...]}}</ref> Hence, dextroethylamphetamine acts as a norepinephrine–dopamine releasing agent (NDRA) with weak effects on serotonin.<ref name="FitzgeraldGannonWalther2024" /><ref name="Nicole2022" />

In terms of structure–activity relationships, the potency of amphetamines as dopamine releasing agents and reuptake inhibitors decreases with increasing ''N''-alkyl chain length.<ref name="ReithBloughHong2015" /> That is, the order of potency of ''N''-alkylated amphetamines is as follows: amphetamine > methamphetamine > ethylamphetamine > propylamphetamine > butylamphetamine.<ref name="ReithBloughHong2015" /> Propylamphetamine is a weak dopamine reuptake inhibitor rather than releaser, whereas butylamphetamine is completely inactive as a dopamine releaser or reuptake inhibitor.<ref name="ReithBloughHong2015" /> The same relationship, for monoamine release and reuptake inhibition generally, has been shown with 4-methylamphetamine and its ''N''-alkylated derivatives like 4-methylmethamphetamine and so forth.<ref name="SolisPartillaSakloth2017">{{cite journal | vauthors = Solis E, Partilla JS, Sakloth F, Ruchala I, Schwienteck KL, De Felice LJ, Eltit JM, Glennon RA, Negus SS, Baumann MH | title = N-Alkylated Analogs of 4-Methylamphetamine (4-MA) Differentially Affect Monoamine Transporters and Abuse Liability | journal = Neuropsychopharmacology | volume = 42 | issue = 10 | pages = 1950–1961 | date = September 2017 | pmid = 28530234 | pmc = 5561352 | doi = 10.1038/npp.2017.98 | url = }}</ref><ref name="Sakloth2015">{{cite thesis | last=Sakloth | first=Farhana | title=Psychoactive synthetic cathinones (or 'bath salts'): Investigation of mechanisms of action | website=VCU Scholars Compass | date=11 December 2015 | doi=10.25772/AY8R-PW77 | url=https://scholarscompass.vcu.edu/etd/4041/ | access-date=24 November 2024}}</ref>

{| class="wikitable" style="font-size:small;" |+ {{Nowrap|Monoamine release of ethylamphetamine and related agents ({{Abbrlink|EC50|Half maximal effective concentration}}, nM)}} |- ! Compound !! data-sort-type="number" | {{abbrlink|NE|Norepinephrine}} !! data-sort-type="number" | {{abbrlink|DA|Dopamine}} !! data-sort-type="number" | {{abbrlink|5-HT|Serotonin}} !! Ref |- | Phenethylamine || 10.9 || 39.5 || >10,000 || <ref name="ReithBloughHong2015" /><ref name="Forsyth2012">{{cite journal | last=Forsyth | first=Andrea N | title=Synthesis and Biological Evaluation of Rigid Analogues of Methamphetamines | website=ScholarWorks@UNO | date=22 May 2012 | url=https://scholarworks.uno.edu/td/1436/ | access-date=4 November 2024}}</ref><ref name="Blough2008">{{cite book | vauthors = Blough B | chapter = Dopamine-releasing agents | veditors = Trudell ML, Izenwasser S | title = Dopamine Transporters: Chemistry, Biology and Pharmacology | pages = 305–320 | date = July 2008 | isbn = 978-0-470-11790-3 | oclc = 181862653 | ol = OL18589888W | publisher = Wiley | location = Hoboken [NJ] | doi = | url = https://books.google.com/books?id=QCagLAAACAAJ | chapter-url = https://bitnest.netfirms.com/external/Books/Dopamine-releasing-agents_c11.pdf }}</ref> |- | ''d''-Amphetamine || 6.6–10.2 || 5.8–24.8 || 698–1,765 || <ref name="RothmanBaumannDersch2001">{{cite journal | vauthors = Rothman RB, Baumann MH, Dersch CM, Romero DV, Rice KC, Carroll FI, Partilla JS | title = Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin | journal = Synapse | volume = 39 | issue = 1 | pages = 32–41 | date = January 2001 | pmid = 11071707 | doi = 10.1002/1098-2396(20010101)39:1<32::AID-SYN5>3.0.CO;2-3 | s2cid = 15573624 }}</ref><ref name="BaumannPartillaLehner2013">{{cite journal | vauthors = Baumann MH, Partilla JS, Lehner KR, Thorndike EB, Hoffman AF, Holy M, Rothman RB, Goldberg SR, Lupica CR, Sitte HH, Brandt SD, Tella SR, Cozzi NV, Schindler CW | title = Powerful cocaine-like actions of 3,4-methylenedioxypyrovalerone (MDPV), a principal constituent of psychoactive 'bath salts' products | journal = Neuropsychopharmacology | volume = 38 | issue = 4 | pages = 552–562 | date = March 2013 | pmid = 23072836 | pmc = 3572453 | doi = 10.1038/npp.2012.204 }}</ref><ref name="Blough2008" /><ref name="PartillaDerschBaumann1999">{{cite book | vauthors = Partilla JS, Dersch CM, Baumann MH, Carroll FI, Rothman RB | chapter = Profiling CNS Stimulants with a High-Throughput Assay for Biogenic Amine Transporter Substrates | title = Problems of Drug Dependence 1999: Proceedings of the 61st Annual Scientific Meeting, The College on Problems of Drug Dependence, Inc | series = NIDA Res Monogr | volume = 180 | pages = 1–476 (252) | date = 1999 | pmid = 11680410 | doi = | url = https://archives.nida.nih.gov/sites/default/files/180.pdf#page=261 | archive-url = https://web.archive.org/web/20230805004105/https://archives.nida.nih.gov/sites/default/files/180.pdf#page=261 | archive-date = August 5, 2023 | quote = RESULTS. Methamphetamine and amphetamine potently released NE (IC50s = 14.3 and 7.0 nM) and DA (IC50s = 40.4 nM and 24.8 nM), and were much less potent releasers of 5-HT (IC50s = 740 nM and 1765 nM). [...] }}</ref> |- | ''d''-Methamphetamine || 12.3–14.3 || 8.5–40.4 || 736–1,292 || <ref name="RothmanBaumannDersch2001" /><ref name="BaumannAyestasPartilla2012">{{cite journal | vauthors = Baumann MH, Ayestas MA, Partilla JS, Sink JR, Shulgin AT, Daley PF, Brandt SD, Rothman RB, Ruoho AE, Cozzi NV | title = The designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue | journal = Neuropsychopharmacology | volume = 37 | issue = 5 | pages = 1192–1203 | date = April 2012 | pmid = 22169943 | pmc = 3306880 | doi = 10.1038/npp.2011.304 }}</ref><ref name="Blough2008" /><ref name="PartillaDerschBaumann1999" /> |- | Ethylamphetamine || {{abbr|ND|No data}} || 88.5 || {{abbr|ND|No data}} || <ref name="ReithBloughHong2015" /> |- | {{nbsp}}{{nbsp}}''d''-Ethylamphetamine || 28.8 || 44.1 || 333.0 || <ref name="FitzgeraldGannonWalther2024">{{cite journal | vauthors = Fitzgerald LR, Gannon BM, Walther D, Landavazo A, Hiranita T, Blough BE, Baumann MH, Fantegrossi WE | title = Structure-activity relationships for locomotor stimulant effects and monoamine transporter interactions of substituted amphetamines and cathinones | journal = Neuropharmacology | volume = 245 | issue = | article-number = 109827 | date = March 2024 | pmid = 38154512 | doi = 10.1016/j.neuropharm.2023.109827 | pmc = 10842458 | url = }}</ref><ref name="Nicole2022">{{cite web | last=Nicole | first=Lauren | title=In vivo Structure-Activity Relationships of Substituted Amphetamines and Substituted Cathinones | date=2022 | website=ProQuest | url=https://www.proquest.com/openview/a207e98868b4a9c5ac9296fb24abbcd8/ | access-date=5 December 2024 | quote = FIGURE 2-6: Release: Effects of the specified test drug on monoamine release by DAT (red circles), NET (blue squares), and SERT (black traingles) in rat brain tissue. [...] EC50 values determined for the drug indicated within the panel. [...]}}</ref> |- | Propylamphetamine || {{abbr|ND|No data}} || {{abbr|RI|Reuptake inhibitor}} (1,013) || {{abbr|ND|No data}} || <ref name="ReithBloughHong2015" /> |- | Butylamphetamine || {{abbr|ND|No data}} || {{abbr|IA|Inactive}} (>10,000) || {{abbr|ND|No data}} || <ref name="ReithBloughHong2015" /> |- | colspan="7" style="width: 1px; background-color:var(--background-color-notice-subtle,#eaecf0); color:inherit; text-align: center;" | '''Notes:''' The smaller the value, the more strongly the drug releases the neurotransmitter. The assays were done in rat brain synaptosomes and human potencies may be different. See also Monoamine releasing agent § Activity profiles for a larger table with more compounds. '''Refs:'''<ref name="RothmanBaumann2003">{{cite journal | vauthors = Rothman RB, Baumann MH | title = Monoamine transporters and psychostimulant drugs | journal = European Journal of Pharmacology | volume = 479 | issue = 1–3 | pages = 23–40 | date = October 2003 | pmid = 14612135 | doi = 10.1016/j.ejphar.2003.08.054 }}</ref><ref name="RothmanBaumann2006">{{cite journal | vauthors = Rothman RB, Baumann MH | title = Therapeutic potential of monoamine transporter substrates | journal = Current Topics in Medicinal Chemistry | volume = 6 | issue = 17 | pages = 1845–1859 | year = 2006 | pmid = 17017961 | doi = 10.2174/156802606778249766 }}</ref> |}

====Other actions==== Ethylamphetamine is inactive as an agonist of the mouse and human trace amine-associated receptor 1 (TAAR1), whereas findings in the case of the rat TAAR1 are conflicting.<ref name="SimmlerBuchyChaboz2016">{{cite journal | vauthors = Simmler LD, Buchy D, Chaboz S, Hoener MC, Liechti ME | title = In Vitro Characterization of Psychoactive Substances at Rat, Mouse, and Human Trace Amine-Associated Receptor 1 | journal = J Pharmacol Exp Ther | volume = 357 | issue = 1 | pages = 134–144 | date = April 2016 | pmid = 26791601 | doi = 10.1124/jpet.115.229765 | url = https://d1wqtxts1xzle7.cloudfront.net/74120533/eae6c6e62565b82d46b4d111bbea0f77b9c2-libre.pdf?1635931703=&response-content-disposition=inline%3B+filename%3DIn_Vitro_Characterization_of_Psychoactiv.pdf&Expires=1746838268&Signature=Sy4fJ90yUhxs68314NxYsW5PAaNrBGePRu35WRR4PIF-3YC7Z~sLdnCn5wfqqbLg9bDEGdt~oW55ugMP3D3jgA0BoRI~~GOb0NQOwrtfUEQK1PQs1uuN9qg5Y1ct8z5NsABm44RgtukkwRMdU6fO7OlfIsQ68hOiFk129Ll7UYqldxD2f1xhE2fTTfsxSpb8cMCJzHn7-ItqLdwnAUPFK7WggDIjmY1kCnaHLwIxMwdJCAq8L6DYzSTg7pZkbR8qlou~GXbTPQt~gYpyZTJp5hgW-7V6K5wLlQ7Z2xE7B0f9wEfuc1W1QNafg125Tr-vvAe4LEGKXV58bnn1bpfWKw__&Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA | archive-url = https://web.archive.org/web/20250509235235/https://d1wqtxts1xzle7.cloudfront.net/74120533/eae6c6e62565b82d46b4d111bbea0f77b9c2-libre.pdf?1635931703=&response-content-disposition=inline%3B+filename%3DIn_Vitro_Characterization_of_Psychoactiv.pdf&Expires=1746838268&Signature=Sy4fJ90yUhxs68314NxYsW5PAaNrBGePRu35WRR4PIF-3YC7Z~sLdnCn5wfqqbLg9bDEGdt~oW55ugMP3D3jgA0BoRI~~GOb0NQOwrtfUEQK1PQs1uuN9qg5Y1ct8z5NsABm44RgtukkwRMdU6fO7OlfIsQ68hOiFk129Ll7UYqldxD2f1xhE2fTTfsxSpb8cMCJzHn7-ItqLdwnAUPFK7WggDIjmY1kCnaHLwIxMwdJCAq8L6DYzSTg7pZkbR8qlou~GXbTPQt~gYpyZTJp5hgW-7V6K5wLlQ7Z2xE7B0f9wEfuc1W1QNafg125Tr-vvAe4LEGKXV58bnn1bpfWKw__&Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA | archive-date = 2025-05-09 }}</ref><ref name="BunzowSondersArttamangkul2001">{{cite journal | vauthors = Bunzow JR, Sonders MS, Arttamangkul S, Harrison LM, Zhang G, Quigley DI, Darland T, Suchland KL, Pasumamula S, Kennedy JL, Olson SB, Magenis RE, Amara SG, Grandy DK | title = Amphetamine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor | journal = Mol Pharmacol | volume = 60 | issue = 6 | pages = 1181–1188 | date = December 2001 | pmid = 11723224 | doi = 10.1124/mol.60.6.1181 | url = }}</ref> In one study, its Ki was 2,500{{nbsp}}nM and its {{Abbrlink|EC50|half-maximal effective concentration}} ({{Abbrlink|Emax|maximal efficacy}}) was 880{{nbsp}}nM (62%) at the rat TAAR1 (i.e., it was a partial agonist), whereas its Ki and/or {{Abbr|EC50|half-maximal effective concentration}} values at the mouse and human TAAR1 were >10,000{{nbsp}}nM.<ref name="SimmlerBuchyChaboz2016" /> In another study however, ethylamphetamine showed very little capacity to activate the rat TAAR1.<ref name="SimmlerBuchyChaboz2016" />

===Pharmacokinetics=== Ethylamphetamine can be ''N''-dealkylated into amphetamine (5–18% excreted in urine after 24{{nbsp}}hours).<ref name="BeckettShenoy1973">{{cite journal | vauthors = Beckett AH, Shenoy EV | title = The effect of N-alkyl chain length of stereochemistry on the absorption, metabolism and during excretion of N-alkylamphetamines in man | journal = J Pharm Pharmacol | volume = 25 | issue = 10 | pages = 793–799 | date = October 1973 | pmid = 4151673 | doi = 10.1111/j.2042-7158.1973.tb09943.x | url = }}</ref> As such, amphetamine may contribute to its effects ''in vivo''.<ref name="BeckettShenoy1973" />

== Chemistry == The molecular structure of ethylamphetamine is analogous to methamphetamine, with an ethyl group in place of the methyl group.<ref group="Note">Amphetamine is a substituted phenethylamine with a methyl group at RA position.</ref> It can also be considered a substituted amphetamine, with an ethyl group on the amphetamine backbone.<ref group="Note">The ethyl group of ethylamphetamine is at RN position, hence the name ''N-ethylamphetamine''.</ref><ref group="Note">Ethylamphetamine is structurally similar to N-methylamphetamine (methamphetamine), the ethyl group being replaced in methamphetamine with a methyl group.</ref>

Analogues of ethylamphetamine include amphetamine, methamphetamine, propylamphetamine, isopropylamphetamine, butylamphetamine, fenfluramine (3-trifluoromethyl-''N''-ethylamphetamine), dimethylamphetamine, and 3-fluoroethamphetamine (3-fluoro-''N''-ethylamphetamine), among others.

== Society and culture == === Recreational use === Ethylamphetamine can be used as a recreational drug and, while its prevalence is less than amphetamine's, it is still encountered as a substance taken for recreational purposes. Ethylamphetamine produces effects similar to amphetamine and methamphetamine, though it is of lower potency.{{cn|date=July 2019}}

== Notes == <references group="Note"/>

== References == {{Reflist}}

Category:Anorectics Category:Designer prodrugs Category:Norepinephrine-dopamine releasing agents Category:Stimulants Category:Substituted amphetamines Category:TAAR1 agonists