Α-Ethyltryptamine

{{Short description|Chemical compound}} {{Lowercase title}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox drug | verifiedrevid = 447115140 | drug_name = α-Ethyltryptamine | INN = Etryptamine | USAN = Etryptamine | image = AET.svg | image_class = skin-invert-image | width = 200px | image2 = Alpha-Ethyltryptamine-3d-sticks.png | image_class2 = bg-transparent | width2 = 235px

| tradename = Monase<ref name="GlennonDukat2023" /> | routes_of_administration = Oral<ref name="GlennonDukat2023" /> | class = Entactogen; Stimulant; Monoamine releasing agent; Serotonin receptor agonist; Monoamine oxidase inhibitor<ref name="GlennonDukat2023" />

| legal_AU =  | legal_BR = F2 | legal_BR_comment = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-07-24 |title=RDC Nº 804 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 804 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-804-de-24-de-julho-de-2023-498447451 |url-status=live |archive-url=https://web.archive.org/web/20230827163149/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-804-de-24-de-julho-de-2023-498447451 |archive-date=2023-08-27 |access-date=2023-08-27 |publisher=Diário Oficial da União |language=pt-BR |publication-date=2023-07-25}}</ref> | legal_CA = Schedule III | legal_US = Schedule I | legal_UK = Class A | legal_DE = Anlage I | legal_UN = P I

| bioavailability = | protein_bound = | metabolism = Hydroxylation<ref name="Barceloux2012" /> | metabolites = • 6-Hydroxy-αET (inactive)<ref name="GlennonDukat2023" /><ref name="Barceloux2012" /> | onset = 0.5–1.5{{nbsp}}hours<ref name="Barceloux2012" /> | elimination_half-life = ~8{{nbsp}}hours<ref name="Barceloux2012" /> | duration_of_action = 6–8{{nbsp}}hours (100–150{{nbsp}}mg)<ref name="Oeri2021" /><ref name="Barceloux2012" /> | excretion = Urine (majority)<ref name="Barceloux2012" />

| CAS_number_Ref = {{cascite|correct|CAS}} | CAS_number = 2235-90-7 | CAS_supplemental = {{CAS|118-68-3}} (acetate) {{CAS|26330-11-0}} (hydrochloride) | ATC_prefix = None | ATC_suffix = | PubChem = 8367 | PubChemSubstance = 46507084 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB01546 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 8064 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = GR181O3R32 | ChEBI = 134838 | ChEMBL = 1619758 | KEGG = D04092 | synonyms = alpha-Ethyltryptamine; αET; AET; α-ET; Etryptamine; PAL-125;<ref name="BloughLandavazo2014" /> 3-(2-Aminobutyl)indole; 3-Indolylbutylamine; U-17312E; U17312E; Ro 3-1932; NSC-63963; NSC-88061

| IUPAC_name = 1-(1''H''-indol-3-yl)butan-2-amine | C=12 | H=16 | N=2 | SMILES = CCC(N)CC1=CNC2=CC=CC=C12 | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C12H16N2/c1-2-10(13)7-9-8-14-12-6-4-3-5-11(9)12/h3-6,8,10,14H,2,7,13H2,1H3 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = ZXUMUPVQYAFTLF-UHFFFAOYSA-N

| melting_point = 222 | melting_high = 223 }}  '''α-Ethyltryptamine''' ('''αET''', '''AET'''), also known as '''etryptamine''', is an entactogen and stimulant drug of the tryptamine family.<ref name="GlennonDukat2023">{{cite journal | vauthors = Glennon RA, Dukat MG | title = α-Ethyltryptamine: A Ratiocinatory Review of a Forgotten Antidepressant | journal = ACS Pharmacology & Translational Science | volume = 6 | issue = 12 | pages = 1780–1789 | date = December 2023 | pmid = 38093842 | doi = 10.1021/acsptsci.3c00139 | pmc = 10714429 }}</ref><ref name="Oeri2021">{{cite journal | vauthors = Oeri HE | title = Beyond ecstasy: Alternative entactogens to 3,4-methylenedioxymethamphetamine with potential applications in psychotherapy | journal = Journal of Psychopharmacology | volume = 35 | issue = 5 | pages = 512–536 | date = May 2021 | pmid = 32909493 | pmc = 8155739 | doi = 10.1177/0269881120920420 }}</ref><ref name="TiHKAL">{{cite book|title=''Tryptamines i Have Known and Loved: The Continuation,''|year=1997|publisher=Transform Press|location=Berkeley, CA|isbn=978-0-9630096-9-2|chapter-url=http://www.erowid.org/library/books_online/tihkal/tihkal11.shtml| vauthors = Shulgin A, Shulgin A |edition=First | author-link=Alexander Shulgin |author2-link=Ann Shulgin|access-date=15 November 2013|chapter-format=Book|chapter="''Part 2, The Chemistry Continues: #11, a-ET: Alpha-Ethyltryptamine; Indole,3-(2-Aminobutyl); Tryptamine,Alpha-Ethyl; 3-(2-Aminobutyl)Indole; Monase," part v, "EXTENSIONS AND COMMENTARY.''"|quote=This base, a-ET or etryptamine, was a promising anti-depressant, explored clinically as the acetate salt by Upjohn under the name of Monase. Its central stimulant activity is probably not due to its monoamineoxidase inhibition activity, but appears to stem from its structural relationship to the indolic psychedelics. It was withdrawn from potential commercial use with the appearance of an unacceptable incidence of a medical condition known as agranulocytosis, but the extra mural research into its action, among the lay population, goes on, [...]}}</ref> It was originally developed and marketed as an antidepressant under the brand name '''Monase''' by Upjohn in the 1960s before being withdrawn due to toxicity.<ref name="GlennonDukat2023" /><ref name="Oeri2021" /><ref name="US3296072">{{ cite patent | country = US | number = 3296072 | status = Patent | title = Method of Treating Mental Depression | pubdate = 1967-01-03 | gdate = 1967-01-03 | fdate = 1964-01-29 | pridate = 1962-06-11 | inventor = Szmuszkovicz J | invent1 = | invent2 = | assign1 = Upjohn Company | postscript = . | assign2 = | class = | url=http://www.google.com/patents/US3296072}}</ref>

Side effects of αET include facial flushing, headache, gastrointestinal distress, insomnia, irritability, appetite loss, and sedation, among others.<ref name="Barceloux2012" /> A rare side effect of αET is agranulocytosis.<ref name="GlennonDukat2023" /><ref name="TiHKAL" /><ref name="Butin1962">{{cite journal | vauthors = Burtin JW | title = Agranulocytosis following Monase therapy | journal = J Kans Med Soc | volume = 63 | issue = | pages = 338–340 | date = August 1962 | pmid = 13875179 | doi = | url = }}</ref> αET acts as a releasing agent of serotonin, norepinephrine, and dopamine, as a weak serotonin receptor agonist, and as a weak monoamine oxidase inhibitor.<ref name="GlennonDukat2023" /><ref name="Oeri2021" /><ref name="BloughLandavazo2014" /> It may also produce serotonergic neurotoxicity.<ref name="GlennonDukat2023" /><ref name="Oeri2021" /><ref name="HuangJohnsonNichols1991" /> αET is a substituted tryptamine and is closely related to α-methyltryptamine (αMT) and other α-alkylated tryptamines.<ref name="GlennonDukat2023" /><ref name="Oeri2021" />

αET was first described in 1947.<ref name="GlennonDukat2023" /><ref name="SnyderKatz1947" /> It was used as an antidepressant for about a year around 1961.<ref name="GlennonDukat2023" /> The drug started being used recreationally in the 1980s and several deaths have been reported.<ref name="GlennonDukat2023" /><ref name="Oeri2021" /><ref name="VarìPichiniGiorgetti2019" /><ref name="Barceloux2012" /> αET is a controlled substance in various countries, including the United States and United Kingdom.<ref name="GlennonDukat2023" /><ref name="VarìPichiniGiorgetti2019" /> There has been renewed interest in αET, for instance as an alternative to MDMA, with the development of psychedelics and entactogens as medicines in the 2020s.<ref name="GlennonDukat2023" /><ref name="Oeri2021" />

==Use and effects== αET was previously used medically as an antidepressant and "psychic energizer" to treat people with depression.<ref name="GlennonDukat2023" /><ref name="Oeri2021" /><ref name="Barceloux2012" /><ref name="TiHKAL" /> It was used for this indication under the brand name Monase.<ref name="GlennonDukat2023" /><ref name="Oeri2021" /><ref name="Barceloux2012" /><ref name="TiHKAL" /> The drug was available pharmaceutically as the acetate salt under the brand name Monase as 15{{nbsp}}mg oral tablets.<ref name="RockyMountainDruggist1961">{{cite book | title=Rocky Mountain Druggist | issue=v. 72 | year=1961 | url=https://books.google.com/books?id=gZd8lzHm9TYC | access-date=6 September 2024 | pages=12, 17 | quote = MONASE--Upjohn Monase 15 mg. Monase, brand of etryptamine acetate is 3-(2-aminobutyl) indole acetate, developed in the Research Laboratories of the Upjohn Company. Each tablet contains etryptamine acetate 15 mg. Monase is indicated in a variety of psychiatric and medical conditions in which mental depression is prominent and for which mood elevation and psychomotor stimulation are considered beneficial. ADMINISTRATION AND DOSAGE: 30 mg. daily in divided doses. SUPPLIED: As coated, compressed tablets, 15 mg., in bottles of 100 and is a prescription product. The catalog number is 3522.}}</ref><ref name="GlennonDukat2023" />

αET is reported to have entactogen and weak psychostimulant effects.<ref name="GlennonDukat2023" /><ref name="Oeri2021" /><ref name="TiHKAL" /> Euphoria, increased energy, openness, and empathy have been specifically reported.<ref name="Oeri2021" /><ref name="GlennonDukat2023" /><ref name="TiHKAL" /> Unlike αMT and other tryptamines, αET is not reported to have psychedelic or hallucinogenic effects.<ref name="Oeri2021" /><ref name="TiHKAL" /> The drug is described as less stimulating and intense than MDMA ("ecstasy") but as otherwise having entactogenic effects resembling those of MDMA.<ref name="Oeri2021" /><ref name="GlennonDukat2023" /> The dose of αET used recreationally has been reported to be 100 to 160{{nbsp}}mg, its onset of action has been reported to be 0.5 to 1.5{{nbsp}}hours, and its duration of action at the preceding doses is described as 6 to 8{{nbsp}}hours.<ref name="GlennonDukat2023" /><ref name="Oeri2021" /><ref name="Barceloux2012" /><ref name="TiHKAL" /> Rapid tolerance to repeated administration of αET has been described.<ref name="TiHKAL" />

==Side effects== Side effects of αET at antidepressant doses have included facial flushing, headache, gastrointestinal distress, insomnia, irritability, and sedation.<ref name="Barceloux2012" /> Additional side effects of αET at recreational doses have included appetite loss and feelings of intoxication.<ref name="Barceloux2012" /> Feelings of lethargy and sedation can occur once the drug wears off.<ref name="Barceloux2012" />

As with many other serotonin releasing agents, toxicity, such as serotonin syndrome, can occur when excessive doses are taken or when combined with certain drugs such as monoamine oxidase inhibitors (MAOIs).<ref name="Gillman2005">{{cite journal | vauthors = Gillman PK | title = Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity | journal = British Journal of Anaesthesia | volume = 95 | issue = 4 | pages = 434–441 | date = October 2005 | pmid = 16051647 | doi = 10.1093/bja/aei210 | quote = Drugs such as MDMA, ecstasy (3,4-methylenedioxymethamphetamine), if combined with MAOIs (including moclobemide) do also cause fatalities because they act as serotonin releasers | doi-access = free }}</ref> Several deaths have been associated with recreational use of αET.<ref name="GlennonDukat2023" /><ref name="VarìPichiniGiorgetti2019">{{cite journal | vauthors = Varì MR, Pichini S, Giorgetti R, Busardò FP | first4=Francesco P. | title=New psychoactive substances—Synthetic stimulants | journal=WIREs Forensic Science | volume=1 | issue=2 | date= March 2019 | issn=2573-9468 | doi=10.1002/wfs2.1197 | article-number=e1197 }}</ref><ref name="Barceloux2012" />

Rarely, agranulocytosis has occurred with prolonged administration of αET at antidepressant doses and has been said to have resulted in several cases and/or deaths.<ref name="GlennonDukat2023" /><ref name="Barceloux2012" /><ref name="Butin1962" />

==Overdose== αET has been administered in clinical studies at doses of up to 300{{nbsp}}mg per day.<ref name="GlennonDukat2023" /><ref name="Barceloux2012" /><ref name="TurnerMerlis1961">{{cite journal | vauthors = Turner WJ, Merlis S | title = Clinical studies with ethyltryptamine | journal = Journal of Neuropsychiatry | volume = 2(Suppl 1) | issue = | pages = 73–76 | date = February 1961 | pmid = 13778759 | doi = | url = }}</ref> An approximate but unconfirmed 700{{nbsp}}mg dose resulted in fatal hyperthermia and agitated delirium in one case.<ref name="GlennonDukat2023" /><ref name="Barceloux2012" /> LD50 doses of αET for various species have been studied and described.<ref name="GlennonDukat2023" /> Treatment of αET intoxication or overdose is supportive.<ref name="Barceloux2012" /> Severe and potentially life-threatening hyperthermia may occur.<ref name="Barceloux2012" /> Serotonergic toxicity associated with serotonergic agents like αET can be managed with benzodiazepines and with the serotonin receptor antagonist cyproheptadine.<ref name="SchifanoNapoletanoChiappini2019">{{cite journal | vauthors = Schifano F, Napoletano F, Chiappini S, Orsolini L, Guirguis A, Corkery JM, Bonaccorso S, Ricciardi A, Scherbaum N, Vento A | title=New Psychoactive Substances (NPS), Psychedelic Experiences and Dissociation: Clinical and Clinical Pharmacological Issues | journal=Current Addiction Reports | volume=6 | issue=2 | date=2019 | issn=2196-2952 | doi=10.1007/s40429-019-00249-z | pages=140–152| hdl=2299/21437 | hdl-access=free }}</ref>

==Interactions== {{See also|MDMA#Interactions|Trip killer#Antidotes of other hallucinogens|MDMA/citalopram}}

==Pharmacology== ===Pharmacodynamics=== Similarly to αMT, αET is a releasing agent of serotonin, norepinephrine and dopamine, with serotonin being the primary neurotransmitter affected.<ref name="GlennonDukat2023" /><ref name="Oeri2021" /><ref name="BloughLandavazo2014">{{cite journal | vauthors = Blough BE, Landavazo A, Partilla JS, Decker AM, Page KM, Baumann MH, Rothman RB | title = Alpha-ethyltryptamines as dual dopamine-serotonin releasers | journal = Bioorganic & Medicinal Chemistry Letters | volume = 24 | issue = 19 | pages = 4754–4758 | date = October 2014 | pmid = 25193229 | pmc = 4211607 | doi = 10.1016/j.bmcl.2014.07.062 }}</ref> It is about 10-fold more potent in inducing serotonin release than in inducing dopamine release and about 28-fold more potent in inducing serotonin release than in inducing norepinephrine release.<ref name="GlennonDukat2023" /><ref name="BloughLandavazo2014" /> The (+)-enantiomer of αET, (+)-αET, is a serotonin–dopamine releasing agent (SDRA) and is one of the few such agents known.<ref name="BloughLandavazo2014" /> It is about 1.7-fold more potent in inducing serotonin release than in inducing dopamine release, about 17-fold more potent in inducing serotonin release than in inducing norepinephrine release, and is about 10-fold more potent in inducing dopamine release than in inducing norepinephrine release.<ref name="BloughLandavazo2014" />

In addition to acting as a monoamine releasing agent, αET acts as a serotonin receptor agonist.<ref name="GlennonDukat2023" /> It is known to act as a weak partial agonist of the serotonin 5-HT2A receptor ({{Abbrlink|EC50|half-maximal effective concentration}} > 10,000{{nbsp}}nM; Emax = 21%).<ref name="GlennonDukat2023" /><ref name="Oeri2021" /><ref name="BloughLandavazo2014" /> (–)-αET is inactive as a 5-HT2A receptor agonist at concentrations of up to 10{{nbsp}}μM, whereas (+)-αET is a 5-HT2A receptor agonist with an EC50 value of 1,250{{nbsp}}nM and an Emax value of 61%.<ref name="BloughLandavazo2014" /> αET has been found to be 150- to 200-fold less potent than αMT as a serotonin receptor agonist in the rat stomach strip.<ref name="BarlowKhan1959">{{cite journal | vauthors = Barlow RB, Khan I | title = Actions of some analogues of tryptamine on the isolated rat uterus and on the isolated rat fundus strip preparations | journal = Br J Pharmacol Chemother | volume = 14 | issue = 1 | pages = 99–107 | date = March 1959 | pmid = 13651585 | pmc = 1481812 | doi = 10.1111/j.1476-5381.1959.tb00934.x | url = }}</ref><ref name="Vane1959">{{cite journal | vauthors = Vane JR | title = The relative activities of some tryptamine analogues on the isolated rat stomach strip preparation | journal = Br J Pharmacol Chemother | volume = 14 | issue = 1 | pages = 87–98 | date = March 1959 | pmid = 13651584 | pmc = 1481817 | doi = 10.1111/j.1476-5381.1959.tb00933.x | url = }}</ref> αET has also been found to have weak affinity for the 5-HT1, 5-HT1E, 5-HT1F, and 5-HT2B receptors.<ref name="GlennonDukat2023" />

{| class="wikitable floatright" style="font-size:small;" |+ Activities of αET, its enantiomers, and related compounds |- ! rowspan="2" | Compound !! colspan="3" | Monoamine release ({{Abbrlink|EC50|half-maximal effective concentration}}, nM) !! colspan="2" | 5-HT2A receptor agonism |- ! Serotonin !! Dopamine !! Norepinephrine !! {{Abbrlink|EC50|half-maximal effective concentration}} (nM) !! Emax (%) |- | Tryptamine || 32.6 ± 2.6 || 164 ± 16 || 716 ± 46 || 7.36 ± 0.56 || 104 ± 4 |- | Serotonin || 44.4 ± 5.3 || >10,000 || >10,000 || {{Abbr|ND|No data}} || {{Abbr|ND|No data}} |- | ''N'',''N''-DMT || 114 ± 15 || >10,000 || 4,166 ± 317 || 38.3 ± 0.81 || 83 ± 0.4 |- | αMT || 21.7 ± 1.0 || 78.6 ± 4.0 || 112 ± 6 || 23.1 ± 2.4 || 103 ± 3 |- | αET || 23.2 ± 1.7 || 232 ± 17 || 640 ± 76a || >10,000 || 21 ± 11 |- | {{nbsp}}{{nbsp}}(–)-αET || 54.9 ± 7.8 || 654 ± 50 || 3,670 ± 1,190a || >10,000 || – |- | {{nbsp}}{{nbsp}}(+)-αET || 34.7 ± 4.9 || 57.6 ± 3.1 || 592 ± 97a || 1,250 ± 310 || 61 ± 8 |- | MDMA || 56.6 ± 2.1 || 376 ± 16 || 77.4 ± 3.4 || {{Abbr|ND|No data}} || {{Abbr|ND|No data}} |- class="sortbottom" | colspan="6" 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 compound produces the effect. '''Footnotes:''' a = αET, (–)-αET, and (+)-αET were norepinephrine partial releasers with Emax values of 78%, 75%, and 71%, respectively. '''Refs:'''<ref name="GlennonDukat2023" /><ref name="BloughLandavazo2014" /><ref name="BloughLandavazoDecker2014">{{cite journal | vauthors = Blough BE, Landavazo A, Decker AM, Partilla JS, Baumann MH, Rothman RB | title = Interaction of psychoactive tryptamines with biogenic amine transporters and serotonin receptor subtypes | journal = Psychopharmacology (Berl) | volume = 231 | issue = 21 | pages = 4135–4144 | date = October 2014 | pmid = 24800892 | pmc = 4194234 | doi = 10.1007/s00213-014-3557-7 | url = }}</ref><ref name="RothmanBaumann2003">{{cite journal | vauthors = Rothman RB, Baumann MH | title = Monoamine transporters and psychostimulant drugs | journal = Eur J Pharmacol | volume = 479 | issue = 1–3 | pages = 23–40 | date = October 2003 | pmid = 14612135 | doi = 10.1016/j.ejphar.2003.08.054 | url = }}</ref> |}

αET is a weak monoamine oxidase inhibitor (MAOI).<ref name="GlennonDukat2023" /><ref name="AskFagervallRoss1983">{{cite journal | vauthors = Ask AL, Fagervall I, Ross SB | title = Selective inhibition of monoamine oxidase in monoaminergic neurons in the rat brain | journal = Naunyn-Schmiedeberg's Archives of Pharmacology | volume = 324 | issue = 2 | pages = 79–87 | date = September 1983 | pmid = 6646243 | doi = 10.1007/BF00497011 }}</ref> It is specifically a selective and reversible inhibitor of monoamine oxidase A (MAO-A).<ref name="GlennonDukat2023" /><ref name="AskFagervallRoss1983" /> An {{Abbrlink|IC50|half-maximal inhibitory concentration}} value of 260{{nbsp}}μM ''in vitro'' and 80 to 100% inhibition of MAO-A at a dose of 10{{nbsp}}mg/kg in rats ''in vivo'' have been reported.<ref name="GlennonDukat2023" /><ref name="Rényi1986">{{cite journal | vauthors = Rényi L | title = The effects of monoamine oxidase inhibitors on the ejaculatory response induced by 5-methoxy-N,N-dimethyltryptamine in the rat | journal = Br J Pharmacol | volume = 88 | issue = 4 | pages = 827–835 | date = August 1986 | pmid = 3091132 | pmc = 1917087 | doi = 10.1111/j.1476-5381.1986.tb16256.x | url = }}</ref> αET is described as slightly more potent as an MAOI than dextroamphetamine.<ref name="GlennonDukat2023" /> Both enantiomers of αET have similar activity as MAOIs, whereas αET's major metabolite 6-hydroxy-αET is inactive.<ref name="GlennonDukat2023" /> The relatively weak MAOI actions of αET have been considered unlikely to be involved in its stimulant, antidepressant, and other psychoactive effects by certain sources.<ref name="GlennonDukat2023" /><ref name="TiHKAL" />

The stimulant effects of αET have been said to lie primarily in (–)-αET, whereas hallucinogenic effects have been said to be present in (+)-αET.<ref name="GlennonDukat2023" /><ref name="Barceloux2012" /> However, these claims appear to be based on animal drug discrimination studies and are not necessarily in accordance with functional studies.<ref name="GlennonDukat2023" /><ref name="BloughLandavazo2014" /> Generalization to {{Abbrlink|DOM|2,5-dimethoxy-4-methylamphetamine}} may have been anomalous and due to the serotonin-releasing actions of αET rather than due to serotonin 5-HT2A receptor activation and associated psychedelic effects.<ref name="GlennonDukat2023" /> Accordingly, αET does not produce the head-twitch response in rodents, unlike known psychedelics.<ref name="GlennonDukat2023" /> However, in another study, low doses of αET (0.5–1.0{{nbsp}}mg/kg) did not produce the head-twitch response but a high dose (5{{nbsp}}mg/kg) did produce the response.<ref name="Younkin_2025">{{cite journal | vauthors = Younkin J, Jones CB, Fiorillo M, Bansode AH, Herszenhorn I, Sarkar N, Artigas A, Dukat M, Gonzalez-Maeso J, Silverman JM | title = Pharmacological Characterization of α-Ethyltryptamine-based 5-HT2A Receptor Agonists for Therapeutic Use (Abstract ID: 190197) | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 392 | issue = 3 | article-number = 103435 | date = 2025 | doi = 10.1016/j.jpet.2025.103435 | url = https://linkinghub.elsevier.com/retrieve/pii/S0022356525396485 | quote = For the in vivo studies using HTR at doses of 0.5, 1 and 5 mg/kg, aET and its isomers showed significant high HTR at only the 5 mg/kg dose as compared to vehicle in C57BL/6 mice. | url-access = subscription }}</ref> Clear hallucinogenic effects of αET have never been documented in humans even at high doses, although the individual enantiomers of αET have never been studied in humans.<ref name="GlennonDukat2023" />

αET has been found to produce serotonergic neurotoxicity similar to that of MDMA and ''para''-chloroamphetamine (PCA) in rats.<ref name="Oeri2021" /><ref name="GlennonDukat2023" /><ref name="HuangJohnsonNichols1991">{{cite journal | vauthors = Huang XM, Johnson MP, Nichols DE | title = Reduction in brain serotonin markers by alpha-ethyltryptamine (Monase) | journal = European Journal of Pharmacology | volume = 200 | issue = 1 | pages = 187–190 | date = July 1991 | pmid = 1722753 | doi = 10.1016/0014-2999(91)90686-k }}</ref> This has included long-lasting reductions in serotonin levels, 5-hydroxyindoleacetic acid (5-HIAA) levels, and serotonin uptake sites in the frontal cortex and hippocampus.<ref name="Oeri2021" /><ref name="HuangJohnsonNichols1991" /> The dosage of αET employed was 8{{nbsp}}doses of 30{{nbsp}}mg/kg by subcutaneous injection with doses spaced by 12-hour intervals.<ref name="Oeri2021" /><ref name="HuangJohnsonNichols1991" /> There are prominent species differences in the neurotoxicity of monoamine releasing agents.<ref name="CapelaCarmoRemião2009">{{cite journal | vauthors = Capela JP, Carmo H, Remião F, Bastos ML, Meisel A, Carvalho F | title = Molecular and cellular mechanisms of ecstasy-induced neurotoxicity: an overview | journal = Mol Neurobiol | volume = 39 | issue = 3 | pages = 210–271 | date = June 2009 | pmid = 19373443 | doi = 10.1007/s12035-009-8064-1 | url = }}</ref><ref name="MoratallaKhairnarSimola2017">{{cite journal | vauthors = Moratalla R, Khairnar A, Simola N, Granado N, García-Montes JR, Porceddu PF, Tizabi Y, Costa G, Morelli M | title = Amphetamine-related drugs neurotoxicity in humans and in experimental animals: Main mechanisms | journal = Prog Neurobiol | volume = 155 | issue = | pages = 149–170 | date = August 2017 | pmid = 26455459 | doi = 10.1016/j.pneurobio.2015.09.011 | url = | hdl = 10261/156486 | hdl-access = free }}</ref> Primates appear to be more susceptible to the damage caused by serotonergic neurotoxins like MDMA than rodents.<ref name="CapelaCarmoRemião2009" />

===Pharmacokinetics=== The absorption of αET appears to be rapid.<ref name="Barceloux2012" /> It has a relatively large volume of distribution.<ref name="Barceloux2012" /> The drug undergoes hydroxylation to form the major metabolite 6-hydroxy-αET (3-(2-aminobutyl)-6-hydroxyindole).<ref name="GlennonDukat2023" /><ref name="Barceloux2012" /> This metabolite is inactive.<ref name="Barceloux2012" /> αET is eliminated primarily in urine and a majority of a dose is excreted in urine within 12 to 24{{nbsp}}hours.<ref name="Barceloux2012" /> Its elimination half-life is approximately 8{{nbsp}}hours.<ref name="Barceloux2012" />

==Chemistry== αET, also known as α-ethyltryptamine or as 3-(2-aminobutyl)indole, is a substituted tryptamine and α-alkyltryptamine derivative.<ref name="TiHKAL" /><ref name="GlennonDukat2023" /><ref name="Oeri2021" />

===Synthesis=== The chemical synthesis of αET has been described.<ref name="TiHKAL" /> It can be synthesised in a two-step synthesis with commercial chemicals via the Henry reaction aka Nitroadol condensation reaction between indole-3-carboxaldehyde and nitropropane under amine salt or ionic liquid catalysis which produces 3-(2-nitrobut-1-enyl)-1''H''-indole, 3-(2-nitrobut-1-enyl)-1''H''-indole can subsequently be reduced via a reducing like lithium aluminum hydride.<ref>{{cite web| vauthors = Anonymous |title= Synthesis of alpha-Methyltryptamine (IT-290/AMT) | work = TheHive |url=https://chemistry.mdma.ch/hiveboard/rhodium/it-290.html|access-date=2 August 2025}}</ref> to form α-ethyltryptamine.

===Analogues=== Analogues of αET include α-methyltryptamine (αMT), α-propyltryptamine (αPT), and other substituted α-alkylated tryptamines like 4-HO-αET, 5-MeO-αET, 5-chloro-αMT (PAL-542), and 5-fluoro-αET (PAL-545).<ref name="TiHKAL" /><ref name="BloughLandavazo2014" />

==History== αET was first described in the scientific literature in 1947.<ref name="GlennonDukat2023" /><ref name="SnyderKatz1947">{{cite journal | vauthors = Snyder HR, Katz L | title = The alkylation of aliphatic nitro compounds with gramine; a new synthesis of derivatives of tryptamine | journal = Journal of the American Chemical Society | volume = 69 | issue = 12 | pages = 3140–3142 | date = December 1947 | pmid = 18919717 | doi = 10.1021/ja01204a061 | bibcode = 1947JAChS..69.3140S }}</ref> The enantiomers of αET were first individually described in 1970.<ref name="GlennonDukat2023" />

Originally believed to exert its effects predominantly via monoamine oxidase inhibition, αET was developed during the 1960s as an antidepressant by Upjohn chemical company in the United States under the generic name etryptamine and the brand name Monase, but was withdrawn from potential commercial use due to incidence of idiosyncratic agranulocytosis in several patients.<ref name="GlennonDukat2023" /><ref name="TiHKAL" /><ref name="Butin1962" /> It was on the market for about a year, around 1961, and was given to more than 5,000{{nbsp}}patients, before being withdrawn.<ref name="GlennonDukat2023" /> αET was usually used as an antidepressant at doses of 30 to 40{{nbsp}}mg/day (but up to 75{{nbsp}}mg/day), which are lower than the doses that have been used recreationally.<ref name="GlennonDukat2023" /><ref name="Oeri2021" />

αET gained limited recreational popularity as a designer drug with MDMA-like effects in the 1980s.<ref name="GlennonDukat2023" /> Subsequently, in the United States it was added to the Schedule I list of illegal substances in 1993 or 1994.<ref name="GlennonDukat2023" /><ref name="TiHKAL" />

==Society and culture== ===Names=== ''Etryptamine'' is the formal generic name of the drug and its {{Abbrlink|INN|International Nonproprietary Name}} and {{Abbrlink|BAN|British Approved Name}}.<ref name="Elks2014">{{cite book | vauthors = Elks J | title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies | publisher=Springer US | year=2014 | isbn=978-1-4757-2085-3 | url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA48 | access-date=2024-09-06 | page=48}}</ref> In the case of the acetate salt, its generic name is ''etryptamine acetate'' and this is its {{Abbrlink|USAN|United States Adopted Name}}.<ref name="Elks2014" /> Etryptamine was used pharmaceutically as etryptamine acetate.<ref name="Elks2014" /><ref name="GlennonDukat2023" /><ref name="RockyMountainDruggist1961" /> Etryptamine is much more well known as ''alpha-ethyltryptamine'' or ''α-ethyltryptamine'' (abbreviated as ''αET'', ''α-ET'', or ''AET'').<ref name="GlennonDukat2023" /><ref name="Oeri2021" /><ref name="TiHKAL" /> Other synonyms of αET and/or its acetate salt include ''3-(2-aminobutyl)indole'', ''3-indolylbutylamine'', ''PAL-125'', ''U-17312E'', ''Ro 3-1932'', ''NSC-63963'', and ''NSC-88061'', as well as its former brand name ''Monase''.<ref name="Elks2014" /><ref name="CAS-αET">{{cite web | title=α-Ethyltryptamine | id = CAS Registry Number 2235-90-7 | website=CAS Common Chemistry | date=6 September 2024 | url=https://commonchemistry.cas.org/detail?cas_rn=2235-90-7 | access-date=6 September 2024}}</ref><ref name="CAS-αET-acetate">{{cite web | title=Etryptamine acetate | id = CAS Registry Number 118-68-3 | website=CAS Common Chemistry | date=6 September 2024 | url=https://commonchemistry.cas.org/detail?cas_rn=118-68-3 | access-date=6 September 2024}}</ref><ref name="BloughLandavazo2014" />

===Recreational use=== αET has been used as a recreational drug since the 1980s.<ref name="GlennonDukat2023" /><ref name="Oeri2021" /><ref name="VarìPichiniGiorgetti2019" /><ref name="Barceloux2012">{{cite book | vauthors = Barceloux DG | title=Medical Toxicology of Drug Abuse: Synthesized Chemicals and Psychoactive Plants | publisher=Wiley | year=2012 | isbn=978-0-471-72760-6 | url=https://books.google.com/books?id=OWFiVaDZnkQC&pg=PA195 | access-date=6 September 2024 | page=195}}</ref> Purported street names include Trip, ET, Love Pearls, and Love Pills.<ref name="GlennonDukat2023" /><ref name="Barceloux2012" />

===Legal status=== ====Canada==== αET (etryptamine) is a Schedule III controlled substance in Canada.<ref name="CDSA">{{cite web | title=Controlled Drugs and Substances Act | website=Department of Justice Canada | url=https://laws-lois.justice.gc.ca/eng/acts/c-38.8/FullText.html | access-date=19 January 2026}}</ref>

====United Kingdom==== αET is a Class A controlled substance in the United Kingdom.<ref name="VarìPichiniGiorgetti2019" />

====United States==== αET is a Schedule I controlled substance in the United States.<ref name="OrangeBook2026">{{citation | title = Orange Book: List of Controlled Substances and Regulated Chemicals (January 2026) | date = January 2026 | publisher = U.S. Department of Justice: Drug Enforcement Administration (DEA): Diversion Control Division | location = United States | url = https://www.deadiversion.usdoj.gov/schedules/orangebook/orangebook.pdf}}</ref><ref name="GlennonDukat2023" />

==Research== Besides depression, αET has been studied in people with schizophrenia and other conditions.<ref name="GlennonDukat2023" />

==References== {{Reflist}}

==External links== * [https://isomerdesign.com/pihkal/explore/5011 AET - Isomer Design] * [https://psychonautwiki.org/wiki/AET AET - PsychonautWiki] * [https://www.erowid.org/chemicals/aet/aet.shtml AET - Erowid] * [https://www.bluelight.org/xf/threads/265132 The Big & Dandy AET Thread - Bluelight] * [http://www.erowid.org/library/books_online/tihkal/tihkal11.shtml α-ET - TiHKAL - Erowid] * [https://isomerdesign.com/pihkal/read/tk/11 α-ET - TiHKAL - Isomer Design]

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