4-Methyl-α-methyltryptamine

{{Drugbox

| verifiedrevid = 458137296

| image = 4-Methyl-AMT.png

| width = 175px

| image2 = 4-Me-AMT.png

| width2 = 175px

| tradename =

| pregnancy_category =

| legal_status = Uncontrolled (but may be covered under the Federal Analogue Act in the United States and under similar bills in other countries)

| routes_of_administration = Oral

| class = Antidepressant

| ATC_prefix = None

| bioavailability =

| metabolism =

| elimination_half-life =

| excretion =

| CAS_number_Ref = {{cascite|correct|CAS}}

| CAS_number = 3569-29-7

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = QY99ES7YWD

| PubChem = 28806639

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 25392939

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 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

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = KEOYEGHPRBDSKD-UHFFFAOYSA-N

| synonyms = 4-Me-αMT; 4-Me-AMT; 4-Methyl-αMT; 4-Methyl-AMT; 4,α-Dimethyltryptamine; 4,α-DMT; MP-809; MP809; Methyl-2-methyltryptamine

| IUPAC_name = 1-methyl-2-(4-methyl-1H-indol-3-yl)-ethylamine

| C=12 | H=16 | N=2

| SMILES = CC(N)Cc2c1c([nH]c2)cccc1C

}}

4-Methyl-α-methyltryptamine (4-Me-αMT or 4-Me-AMT), also known as 4,α-dimethyltryptamine (4,α-DMT) and by its developmental code name MP-809, is an experimental antidepressant of the tryptamine and α-alkyltryptamine families.{{cite book | author1=Abram Hoffer | author2=Humphrey Osmond | title=The Hallucinogens | chapter=Indole Hallucinogens Derived from Tryptophan | pages=443–516 (468) | chapter-url=https://bitnest.netfirms.com/external/Books/TheHallucinogens#page=451 | publisher=Elsevier | date=1967 | isbn=978-1-4832-3296-6 | doi=10.1016/b978-1-4832-3296-6.50008-2 | lccn=66030086 | oclc=332437 | ol=OL35255701M | url=https://bitnest.netfirms.com/external/Books/TheHallucinogens | quote=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.}}{{cite book | veditors=Gordon M | title=Psychopharmacological Agents: Use, Misuse and Abuse | series=Medicinal Chemistry: A Series of Monographs | volume=4 | vauthors = Shulgin AT | chapter=Psychotomimetic Agents | date=1976 | isbn=978-0-12-290559-9 | doi=10.1016/b978-0-12-290559-9.50011-9 | pages=59–146 | publisher=Academic Press | chapter-url=https://bitnest.netfirms.com/external/10.1016/B978-0-12-290559-9.50011-9 | quote=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.}}{{cite book | vauthors = Shulgin AT | chapter = Hallucinogens | pages = 1109–1137 | chapter-url = https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=6ac0c892ee380436f614d3aae0686ef617b2e0c5 | veditors = Burger A, Wolf ME | title = Burger's Medicinal Chemistry | edition = 4 | volume = 3 | date = 1980 | publisher = Wiley | location = New York | isbn = 978-0-471-01572-7 | oclc = 219960627 | url = https://books.google.com/books?id=2b3wAAAAMAAJ | quote = 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.}}{{cite journal | vauthors = McKenna DJ, Towers GH | title = Biochemistry and pharmacology of tryptamines and beta-carbolines. A minireview | journal = J Psychoactive Drugs | volume = 16 | issue = 4 | pages = 347–358 | date = 1984 | pmid = 6394730 | doi = 10.1080/02791072.1984.10472305 | url = https://bitnest.netfirms.com/external/10.1080/02791072.1984.10472305| url-access = subscription }}{{cite journal | vauthors = Azima H, Arthurs D, Silver A, Azima FJ | title = The effect of MP-809 in depressive states: a multi-blind study | journal = The American Journal of Psychiatry | volume = 119 | issue = 6 | pages = 573–574 | date = December 1962 | pmid = 13965759 | doi = 10.1176/ajp.119.6.573 }}{{cite journal | vauthors = Brodey JF, Steiner WG, Himwich HE | title = An electrographic study of psilocin and 4-methyl-alpha-methyl tryptamine (MP-809) | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 140 | pages = 8–18 | date = April 1963 | pmid = 14015664 | doi = 10.1016/S0022-3565(25)26511-9}} It is closely structurally related to serotonergic psychedelics and entactogens like α-methyltryptamine (αMT) and α-ethyltryptamine (αET). 4-Me-αMT was investigated as an antidepressant by Sandoz in Canada in the early 1960s, although it was never marketed.

Dosage and effects

It is active at a dosage of 20 to 60{{nbsp}}mg orally in humans, though described as being an antidepressant rather than a hallucinogen. It was found to be effective as an antidepressant in preliminary clinical studies. Alexander Shulgin has said that 4-Me-αMT produced some feelings of unreality at a dose of 20{{nbsp}}mg, as well as skin flushing, muscle tightness, and mydriasis.{{cite book | vauthors = Shulgin AT | chapter=Basic Pharmacology and Effects | pages=67–137 | veditors = Laing RR | title=Hallucinogens: A Forensic Drug Handbook | publisher=Elsevier Science | series=Forensic Drug Handbook Series | year=2003 | isbn=978-0-12-433951-4 | url=https://books.google.com/books?id=l1DrqgobbcwC | chapter-url=https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=6bb3a7499da8e9852b39cd4db16891147c83f5c6 | access-date=1 February 2025 | quote = 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.}}{{cite book | author1 = Alexander T. Shulgin | author2 = Ann Shulgin | title = TiHKAL: The Continuation | publisher = Transform Press | date = 1997 | edition = 1st | location = Berkeley, CA | isbn = 978-0-9630096-9-2 | oclc = 38503252 | url = https://books.google.com/books?id=jl_ik66IumUC | quote = 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.}} However, he has said that it could not be called a hallucinogen at assessed doses and has listed the hallucinogenic dosage as being greater than 60{{nbsp}}mg.{{cite journal | vauthors = Jacob P, Shulgin AT | title = Structure-activity relationships of the classic hallucinogens and their analogs | journal = NIDA Res Monogr | volume = 146 | issue = | pages = 74–91 | date = 1994 | pmid = 8742795 | doi = | url = https://archives.nida.nih.gov/sites/default/files/monograph146.pdf#page=79}}

Pharmacology

4-Me-αMT partially reverses reserpine-induced behavioral depression in rodents (by up to 60%), but does not produce hyperlocomotion.{{cite journal | vauthors = Kalir A, Szara S | title = Synthesis and pharmacological activity of alkylated tryptamines | journal = J Med Chem | volume = 9 | issue = 3 | pages = 341–344 | date = May 1966 | pmid = 5960901 | doi = 10.1021/jm00321a017 | url = https://bitnest.netfirms.com/external/10.1021/jm00321a017| url-access = subscription }} This was the case at a dose of 50{{nbsp}}mg/kg, whereas αMT produced clear hyperlocomotion and near-fully reversed reserpine-induced hypoactivity (by 95%) at a dose of 15{{nbsp}}mg/kg. Hence, 4-Me-αMT shows reduced antidepressant- and psychostimulant-like potency compared to αMT. It is also less active than αET. The drug is said to have very weak monoamine oxidase inhibition.