4-Methyl-α-methyltryptamine

Drug belonging to the tryptamine class From Wikipedia, the free encyclopedia

4-Me-αMT (developmental code name MP-809), or 4-Me-AMT, also known as 4-methyl-α-methyltryptamine or as 4,α-dimethyltryptamine (4,α-DMT), is an experimental antidepressant of the tryptamine and α-alkyltryptamine families that was never marketed.^[3]^[4]^[5]^[1]^[6]^[7] It is closely structurally related to serotonergic psychedelics and entactogens like α-methyltryptamine (αMT) and α-ethyltryptamine (αET).^[1]

Other names4-Me-αMT; 4-Me-AMT; 4-Methyl-αMT; 4-Methyl-AMT; 4,α-Dimethyltryptamine; 4,α-DMT; MP-809; MP809; Methyl-2-methyltryptamine

Routes of
administrationOral^[1]^[2]

Drug classAntidepressant

ATC code

None

Quick facts Clinical data, Other names ...

4-Me-αMT
Clinical data


Other names	4-Me-αMT; 4-Me-AMT; 4-Methyl-αMT; 4-Methyl-AMT; 4,α-Dimethyltryptamine; 4,α-DMT; MP-809; MP809; Methyl-2-methyltryptamine
Routes of administration	Oral^[1]^[2]
Drug class	Antidepressant
ATC code	None
Legal status
Legal status	Uncontrolled (but may be covered under the Federal Analogue Act in the United States and under similar bills in other countries)
Identifiers
IUPAC name 1-methyl-2-(4-methyl-1H-indol-3-yl)-ethylamine
CAS Number	3569-29-7^Y
PubChem CID	28806639
ChemSpider	25392939^Y
UNII	QY99ES7YWD
CompTox Dashboard (EPA)	DTXSID70708203
Chemical and physical data
Formula	C₁₂H₁₆N₂
Molar mass	188.274 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES CC(N)Cc2c1c([nH]c2)cccc1C
InChI InChI=1S/C12H16N2/c1-8-4-3-5-11-12(8)10(7-14-11)6-9(2)13/h3-5,7,9,14H,6,13H2,1-2H3^Y Key:KEOYEGHPRBDSKD-UHFFFAOYSA-N^Y
(verify)

Use and effects

4-Me-αMT is active at a dose of 20 to 60 mg orally in humans, though described as being an antidepressant rather than a hallucinogen.^[1]^[2] It was found to be effective as an antidepressant in preliminary clinical studies.^[3]^[6] Alexander Shulgin has said that 4-Me-αMT produced some feelings of unreality at 20 mg, as well as skin flushing, muscle tightness, and mydriasis.^[2]^[8] However, he has said that it could not be called a hallucinogen at assessed doses^[2] and has listed the hallucinogenic dose as being greater than 60 mg.^[9]

Interactions

Pharmacology

Pharmacodynamics

4-Me-αMT partially reverses reserpine-induced behavioral depression in rodents (by up to 60%), but does not produce hyperlocomotion.^[6]^[10] This was the case at a dose of 50 mg/kg, whereas αMT produced clear hyperlocomotion and near-fully reversed reserpine-induced hypoactivity (by 95%) at a dose of 15 mg/kg.^[10] Hence, 4-Me-αMT shows reduced antidepressant- and psychostimulant-like potency compared to αMT.^[10] It is also less active than αET.^[10] The drug is said to have very weak monoamine oxidase inhibition.^[3]^[6]

Chemistry

Analogues

Analogues of 4-methyl-AMT include α-methyltryptamine (AMT), 4-methyl-AET, 4-methyl-DMT, 4-HO-AMT, 4-HO-AET, and RS134-49 (4-methyl-THPI), among others.

History

4-Me-αMT was first described in the scientific literature by 1962.^[6] It was investigated as an antidepressant by Sandoz in Canada in the early 1960s, although it was never marketed.^[3]^[1]^[6]^[7]

References

[1]
McKenna DJ, Towers GH (1984). "Biochemistry and pharmacology of tryptamines and beta-carbolines. A minireview". J Psychoactive Drugs. 16 (4): 347–358. doi:10.1080/02791072.1984.10472305. PMID 6394730.
[2]
Shulgin AT (2003). "Basic Pharmacology and Effects". In Laing RR (ed.). Hallucinogens: A Forensic Drug Handbook. Forensic Drug Handbook Series. Elsevier Science. pp. 67–137. ISBN 978-0-12-433951-4. Retrieved 1 February 2025. Three related compounds deserve specific mention. The 4-methyl homologue of α-MT, α,4-dimethyltryptamine (α,4-DMT), is orally active in humans at 20mg and produces some feelings of unreality, with neurological toxicity including skin flushing and eye dilation. The 4-hydroxy analogue (4-HO-α-MT) has been observed by some to evoke visual changes, accompanied by dizziness and mild depression. In the 15—20mg range (orally) there is occasional tachycardia, headache, and diarrhea. And the complete relocation of the 3-(2-aminopropyl)-chain of α- MT to the 5-position creates an isomer called 5-IT which, with orally produces a state of increased heart rate, anorexia, diuresis and slight hyperthermia, all lasting about 12 hours. None of these materials could be called hallucinogens.
[3]
Abram Hoffer, Humphrey Osmond (1967). "Indole Hallucinogens Derived from Tryptophan". The Hallucinogens. Elsevier. pp. 443–516 (468). doi:10.1016/b978-1-4832-3296-6.50008-2. ISBN 978-1-4832-3296-6. LCCN 66030086. OCLC 332437. OL 35255701M. Methyl-2-methyltryptamine [4-methyl-α-methyltryptamine]: Methyl-2-methyltryptamine is one of the newer antidepressants which was tested by Sandoz in Canada. The 4-substituted indoles are interesting compounds and it is not surprising this compound was active. Its LD-50 for mice was 55 mg/kg given intravenously and 90 mg/kg given subcutaneously. The LD-50 for rabbits given intravenously was 6 mg/kg. It was less toxic than IT-290. The 4-methyl derivative was a weak monoamine oxidase inhibitor. In rats it abolished the reserpine effect but had less synergistic effect with 5-hydroxytryptophan and a-dopa than did Catron. Preliminary clinical investigations showed it was an antidepressant and was beneficial in two thirds of a small group of neurotic patients.
[4]
Shulgin AT (1976). "Psychotomimetic Agents". In Gordon M (ed.). Psychopharmacological Agents: Use, Misuse and Abuse. Medicinal Chemistry: A Series of Monographs. Vol. 4. Academic Press. pp. 59–146. doi:10.1016/b978-0-12-290559-9.50011-9. ISBN 978-0-12-290559-9. A single mention has been made of the antidepressant utility of a ring-substituted homolog, 4α-dimethyltryptamine (XXV), but no details are presented (Hoffer and Osmond, 1967b). [...] Hoffer, A., and Osmond, H. (1967b). "The Hallucinogens," p. 468. Academic Press, New York.
[5]
Shulgin AT (1980). "Hallucinogens". In Burger A, Wolf ME (eds.). Burger's Medicinal Chemistry. Vol. 3 (4 ed.). New York: Wiley. pp. 1109–1137. ISBN 978-0-471-01572-7. OCLC 219960627. A number of isomers and homologs of these alkylated tryptamines have been evaluated in clinical studies. The homologation of the α-methyl group of 60.29j to an ethyl radical results in a drug that has been employed experimentally as an antidepressant under the trade name of Monase (60.30, 129). It is considerably less potent than 60.29j, with dosages of 150 mg needed to produce a talkative intoxication. The addition of a methyl group at the 4 position yields α,4-dimethyltryptamine,60.31, which has also been reported to have antidepressant properties, but there are no experimental details given (131). [...] 131. A. Hoffer and H. Osmond. The Hallucinogens, Academic. New York. 1967. p. 468.
[6]
Azima H, Arthurs D, Silver A, Azima FJ (December 1962). "The effect of MP-809 in depressive states: a multi-blind study". The American Journal of Psychiatry. 119 (6): 573–574. doi:10.1176/ajp.119.6.573. PMID 13965759.
[7]
Brodey JF, Steiner WG, Himwich HE (April 1963). "An electrographic study of psilocin and 4-methyl-alpha-methyl tryptamine (MP-809)". The Journal of Pharmacology and Experimental Therapeutics. 140: 8–18. doi:10.1016/S0022-3565(25)26511-9. PMID 14015664.
[8]
Alexander T. Shulgin, Ann Shulgin (1997). TiHKAL: The Continuation (1st ed.). Berkeley, CA: Transform Press. ISBN 978-0-9630096-9-2. OCLC 38503252. The analogue with the methyl group relocated to the indolic 4-position (4,α-DMT) has been looked at in man. At an oral dose of 20 milligrams, there are reports of feelings of unreality. External body signs include flushing, muscle tightness, and eye dilation.
[9]
Jacob P, Shulgin AT (1994). "Structure-activity relationships of the classic hallucinogens and their analogs" (PDF). NIDA Res Monogr. 146: 74–91. PMID 8742795. Archived from the original (PDF) on August 5, 2023.
[10]
Kalir A, Szara S (May 1966). "Synthesis and pharmacological activity of alkylated tryptamines". J Med Chem. 9 (3): 341–344. doi:10.1021/jm00321a017. PMID 5960901.