Α-Ethyltryptamine

αET was previously used medically as an antidepressant and "psychic energizer" to treat people with depression. It was used for this indication under the brand name Monase.

αET was available pharmaceutically as the acetate salt under the brand name Monase in the form of 15{{nbsp}}mg oral tablets.{{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.}}

αET is reported to have entactogen and weak psychostimulant effects. Euphoria, increased energy, openness, and empathy have been specifically reported. Unlike αMT and other tryptamines, αET is not reported to have psychedelic or hallucinogenic effects. The drug is described as less stimulating and intense than MDMA ("ecstasy") but as otherwise having entactogenic effects resembling those of MDMA. 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. Rapid tolerance to repeated administration of αET has been described.

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

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).{{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 }} Several deaths have been associated with recreational use of αET.{{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 | page=}}

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.

αET has been administered in clinical studies at doses of up to 300{{nbsp}}mg per day.{{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 = }} An approximate but unconfirmed 700{{nbsp}}mg dose resulted in fatal hyperthermia and agitated delirium in one case. LD₅₀ doses of αET for various species have been studied and described. Treatment of αET intoxication or overdose is supportive. Severe and potentially life-threatening hyperthermia may occur. Serotonergic toxicity associated with serotonergic agents like αET can be managed with benzodiazepines and with the serotonin receptor antagonist cyproheptadine.{{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 }}

Similarly to αMT, αET is a releasing agent of serotonin, norepinephrine and dopamine, with serotonin being the primary neurotransmitter affected.{{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 }} 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. The (+)-enantiomer of αET, (+)-αET, is a serotonin–dopamine releasing agent (SDRA) and is one of the few such agents known. 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.

In addition to acting as a monoamine releasing agent, αET acts as a serotonin receptor agonist. It is known to act as a weak partial agonist of the serotonin 5-HT_2A receptor ({{Abbrlink|EC₅₀|half-maximal effective concentration}} > 10,000{{nbsp}}nM; E_max = 21%). (–)-αET is inactive as a 5-HT_2A receptor agonist at concentrations of up to 10{{nbsp}}μM, whereas (+)-αET is a 5-HT_2A receptor agonist with an EC₅₀ value of 1,250{{nbsp}}nM and an E_max value of 61%. αET has also been found to have weak affinity for the 5-HT₁, 5-HT_1E, 5-HT_1F, and 5-HT_2B receptors.

αET is a weak monoamine oxidase inhibitor (MAOI).{{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 }} It is specifically a selective and reversible inhibitor of monoamine oxidase A (MAO-A). 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.{{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 = }} αET is described as slightly more potent as an MAOI than dextroamphetamine. Both enantiomers of αET have similar activity as MAOIs, whereas αET's major metabolite 6-hydroxy-αET is inactive. 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.

The stimulant effects of αET have been said to lie primarily in (–)-αET, whereas hallucinogenic effects have been said to be present in (+)-αET. However, these claims appear to be based on animal drug discrimination studies and are not necessarily in accordance with functional studies. 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-HT_2A receptor activation and associated psychedelic effects. Accordingly, αET does not produce the head-twitch response in rodents, unlike known psychedelics. In addition, 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.

αET has been found to produce serotonergic neurotoxicity similar to that of MDMA and para-chloroamphetamine (PCA) in rats.{{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 }} 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. The dosage of αET employed was 8{{nbsp}}doses of 30{{nbsp}}mg/kg by subcutaneous injection with doses spaced by 12-hour intervals. There are prominent species differences in the neurotoxicity of monoamine releasing agents.{{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 = }}{{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 }} Primates appear to be more susceptible to the damage caused by serotonergic neurotoxins like MDMA than rodents.

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

αET, also known as 3-(2-aminobutyl)indole, is a substituted tryptamine and α-alkyltryptamine derivative. Analogues of αET include α-methyltryptamine (αMT) and other substituted α-alkylated tryptamines like 5-MeO-αET, 5-chloro-αMT (PAL-542), and 5-fluoro-αET (PAL-545).

αET was first described in the scientific literature in 1947.{{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 }} The enantiomers of αET were first individually described in 1970.

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. It was on the market for about a year, around 1961, and was given to more than 5,000{{nbsp}}patients, before being withdrawn. 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.

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

Etryptamine is the formal generic name of the drug and its {{Abbrlink|INN|International Nonproprietary Name}} and {{Abbrlink|BAN|British Approved Name}}.{{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}} In the case of the acetate salt, its generic name is etryptamine acetate and this is its {{Abbrlink|USAN|United States Adopted Name}}. Etryptamine was used pharmaceutically as etryptamine acetate. Etryptamine is much more well known as alpha-ethyltryptamine or α-ethyltryptamine (abbreviated as αET, α-ET, or AET). 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.{{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}}{{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}}

αET has been used as a recreational drug since the 1980s.{{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}} Purported street names include Trip, ET, Love Pearls, and Love Pills.

αET is a Schedule I controlled substance in the United States and a Class A controlled substance in the United Kingdom.

Besides depression, αET has been studied in people with schizophrenia and other conditions.

{{Reflist}}

• [http://www.erowid.org/library/books_online/tihkal/tihkal11.shtml #11. α-ET - TiHKAL - Erowid]
• [https://isomerdesign.com/pihkal/read/tk/11 #11 α-ET - TiHKAL - isomer design]
• [http://www.erowid.org/chemicals/aet/ AET - Erowid]

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