Wikipedia

α-Ethyltryptamine

α-Ethyltryptamine (αET, AET), also known as etryptamine, is an entactogen and stimulant drug of the tryptamine family.[4][3][5][6] 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originally developed and marketed as an antidepressant under the brand name Monase by Upjohn in the 1960s before being withdrawn due to toxicity.[4][3][7]

α-Ethyltryptamine
INN: Etryptamine
Clinical data
Trade namesMonase
Other namesalpha-Ethyltryptamine; αET; AET; α-ET; Etryptamine; PAL-125;[1] 3-(2-Aminobutyl)indole; 3-Indolylbutylamine; U-17312E; Ro 3-1932; NSC-63963; NSC-88061, Etryptamine (USAN US)
Routes of
administration		Oral
Drug classEntactogen; Stimulant; Monoamine releasing agent; Serotonin receptor agonist; Monoamine oxidase inhibitor
ATC code
  • None
Legal status
Legal status
Pharmacokinetic data
Duration of action6–8 hours (100–150 mg)[3]
Identifiers
  • 1-(1H-indol-3-yl)butan-2-amine
CAS Number
PubChem CID
PubChem SID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC12H16N2
Molar mass188.274 g·mol−1
3D model (JSmol)
Melting point222 to 223 °C (432 to 433 °F)
  • CCC(N)CC1=CNC2=CC=CC=C12
  • InChI=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 checkY
  • Key:ZXUMUPVQYAFTLF-UHFFFAOYSA-N checkY
  (verify)

A rare side effect of αET is agranulocytosis.[4][6] αET acts as a releasing agent of serotonin, norepinephrine, and dopamine, as a serotonin receptor agonist, and as a monoamine oxidase inhibitor.[4][3][1] It may also produce serotonergic neurotoxicity.[4][3][8] αET is a substituted tryptamine and is closely related to α-methyltryptamine (αMT).[4][3]

αET was first described in 1947.[4][9] It is a controlled substance in various countries, including the United States and United Kingdom.[4][10] It has been used recreationally and deaths have been reported.[4][3][10] 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.[4][3]

Effects

edit

αET is reported to have antidepressant, psychostimulant, and entactogen effects.[4][3] Euphoria, openness, empathy, and sedation are also reported.[3] Unlike αMT and other tryptamines, αET is not generally reported to have psychedelic or hallucinogenic effects.[3][6] The drug is described as less stimulating and intense than MDMA ("ecstasy") but as otherwise having entactogenic effects resembling those of this drug.[3] The dose of αET used recreationally has been reported to be 100 to 150 mg and its duration of action at these doses is described as 6 to 8 hours.[3]

Side effects

edit

Several deaths have been associated with αET.[10]

Overdose

edit

αET has been administered in clinical studies at doses of up to 300 mg.[4]

Pharmacology

edit

Similarly to αMT, αET is a releasing agent of serotonin, norepinephrine and dopamine, with serotonin being the primary neurotransmitter affected.[4][3][1] The (+)-enantiomer of αET, (+)-αET, is a serotonin–dopamine releasing agent (SDRA) and is one of the few such agents known.[1]

In addition to acting as a monoamine releasing agent, αET acts as a non-selective serotonin receptor agonist.[citation needed] It is known to act as a weak partial agonist of the serotonin 5-HT2A receptor (EC50Tooltip half-maximal effective concentration > 10,000 nM; Emax = 21%).[3][1] (–)-αET is inactive as a 5-HT2A receptor agonist at up to 10 μM, whereas (+)-αET is a 5-HT2A receptor agonist with an EC50 value of 1,250 nM and an Emax value of 61%.[1]

αET is also a monoamine oxidase inhibitor (MAOI).[11] It is specifically a selective and reversible inhibitor of monoamine oxidase A (MAO-A).[11]

A study performed in 1991 with rats provided evidence that αET may induce serotonergic neurotoxicity similar to that of MDMA.[3][4][8] 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 other MAOIs.[12]

Chemistry

edit

αET, also known as 3-(2-aminobutyl)indole, is a substituted tryptamine and α-alkyltryptamine derivative.[4][3] 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).[1]

History

edit

αET was first described in the scientific literature in 1947.[4][9] Originally believed to exert its effects predominantly via monoamine oxidase inhibition, it was developed during the 1960s as an antidepressant by Upjohn chemical company in the United States under the name Monase, but was withdrawn from potential commercial use due to incidence of idiosyncratic agranulocytosis in several patients.[4][6] It was on the market for about a year, around 1961, and was given to more than 5,000 patients, before being withdrawn.[4] It was used as an antidepressant at doses of 30 to 40 mg/day, which are lower than recreationally employed doses.[4][3]

αET gained limited recreational popularity as a designer drug in the 1980s. Subsequently, in the United States it was added to the Schedule I list of illegal substances in 1993.[citation needed]

Society and culture

edit

Names

edit

Etryptamine is the formal generic name of the drug and its INNTooltip International Nonproprietary Name and BANTooltip British Approved Name.[13] In the case of the acetate salt, its generic name is etryptamine acetate and this is its USANTooltip United States Adopted Name.[13] Etryptamine was used pharmaceutically as etryptamine acetate.[13] Etryptamine is much more well-known as alpha-ethyltryptamine or α-ethyltryptamine (abbreviated as αET, α-ET, or AET).[4][3][6] 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.[13][14][15][1]

edit

αET is a Schedule I controlled substance in the United States and a Class A controlled substance in the United Kingdom.[4][10]

References

edit
  1. ^ a b c d e f g h Blough BE, Landavazo A, Partilla JS, Decker AM, Page KM, Baumann MH, et al. (October 2014). "Alpha-ethyltryptamines as dual dopamine-serotonin releasers". Bioorganic & Medicinal Chemistry Letters. 24 (19): 4754–4758. doi:10.1016/j.bmcl.2014.07.062. PMC 4211607. PMID 25193229.
  2. ^ Anvisa (2023-07-24). "RDC Nº 804 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 804 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-07-25). Archived from the original on 2023-08-27. Retrieved 2023-08-27.
  3. ^ a b c d e f g h i j k l m n o p q r s Oeri HE (May 2021). "Beyond ecstasy: Alternative entactogens to 3,4-methylenedioxymethamphetamine with potential applications in psychotherapy". Journal of Psychopharmacology. 35 (5): 512–536. doi:10.1177/0269881120920420. PMC 8155739. PMID 32909493.
  4. ^ a b c d e f g h i j k l m n o p q r s t u Glennon RA, Dukat MG (December 2023). "α-Ethyltryptamine: A Ratiocinatory Review of a Forgotten Antidepressant". ACS Pharmacology & Translational Science. 6 (12): 1780–1789. doi:10.1021/acsptsci.3c00139. PMC 10714429. PMID 38093842.
  5. ^ "AET (alpha-ethyltryptamine)". Erowid Vault.
  6. ^ a b c d e Shulgin A, Shulgin A (1997). ""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."" (Book). Tryptamines i Have Known and Loved: The Continuation, (First ed.). Berkeley, CA: Transform Press. ISBN 978-0-9630096-9-2. Retrieved 15 November 2013. 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, [...]
  7. ^ US Patent 3296072, Szmuszkovicz J, "Method of Treating Mental Depression", published 1967-01-03, issued 1967-01-03, assigned to Upjohn Company. 
  8. ^ a b Huang XM, Johnson MP, Nichols DE (July 1991). "Reduction in brain serotonin markers by alpha-ethyltryptamine (Monase)". European Journal of Pharmacology. 200 (1): 187–190. doi:10.1016/0014-2999(91)90686-k. PMID 1722753.
  9. ^ a b Snyder HR, Katz L (December 1947). "The alkylation of aliphatic nitro compounds with gramine; a new synthesis of derivatives of tryptamine". Journal of the American Chemical Society. 69 (12): 3140–3142. doi:10.1021/ja01204a061. PMID 18919717.
  10. ^ a b c d Varì MR, Pichini S, Giorgetti R, Busardò FP (March 2019). "New psychoactive substances—Synthetic stimulants". WIREs Forensic Science. 1 (2). doi:10.1002/wfs2.1197. ISSN 2573-9468.
  11. ^ a b Ask AL, Fagervall I, Ross SB (September 1983). "Selective inhibition of monoamine oxidase in monoaminergic neurons in the rat brain". Naunyn-Schmiedeberg's Archives of Pharmacology. 324 (2): 79–87. doi:10.1007/BF00497011. PMID 6646243.
  12. ^ Gillman PK (October 2005). "Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity". British Journal of Anaesthesia. 95 (4): 434–441. doi:10.1093/bja/aei210. PMID 16051647. Drugs such as MDMA, ecstasy (3,4-methylenedioxymethamphetamine), if combined with MAOIs (including moclobemide) do also cause fatalities because they act as serotonin releasers
  13. ^ a b c d Elks J (2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer US. p. 48. ISBN 978-1-4757-2085-3. Retrieved 2024-09-06.
  14. ^ "α-Ethyltryptamine". CAS Common Chemistry. 6 September 2024. CAS Registry Number 2235-90-7. Retrieved 6 September 2024.
  15. ^ "Etryptamine acetate". CAS Common Chemistry. 6 September 2024. CAS Registry Number 118-68-3. Retrieved 6 September 2024.
edit
Retrieved from "https://en.wikipedia.org/w/index.php?title=Α-Ethyltryptamine&oldid=1244287036"