2-Methyltryptamine

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| class = Serotonin receptor agonist

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| CAS_number = 2731-06-8

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| PubChem = 75949

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| ChemSpiderID = 68452

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| ChEMBL = 2358910

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| synonyms = 2-MT; 2-Me-T; 2-Methyl-T

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

| C=11 | H=14 | N=2

| SMILES = CC1=C(C2=CC=CC=C2N1)CCN

| StdInChI = 1S/C11H14N2/c1-8-9(6-7-12)10-4-2-3-5-11(10)13-8/h2-5,13H,6-7,12H2,1H3

| StdInChIKey = CPVSLHQIPGTMLH-UHFFFAOYSA-N

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2-Methyltryptamine (2-MT, 2-Me-T, or 2-methyl-T) is a serotonin receptor agonist of the tryptamine family.{{cite journal | vauthors = Abiero A, Ryu IS, Botanas CJ, Custodio RJ, Sayson LV, Kim M, Lee HJ, Kim HJ, Seo JW, Cho MC, Lee KW, Yoo SY, Jang CG, Lee YS, Cheong JH | title = Four Novel Synthetic Tryptamine Analogs Induce Head-Twitch Responses and Increase 5-HTR2a in the Prefrontal Cortex in Mice | journal = Biomolecules & Therapeutics | volume = 28 | issue = 1 | pages = 83–91 | date = January 2020 | pmid = 31230432 | pmc = 6939696 | doi = 10.4062/biomolther.2019.049 }}{{cite journal | vauthors = Chen X, Li J, Yu L, Maule F, Chang L, Gallant JA, Press DJ, Raithatha SA, Hagel JM, Facchini PJ | title = A cane toad (Rhinella marina) N-methyltransferase converts primary indolethylamines to tertiary psychedelic amines | journal = The Journal of Biological Chemistry | volume = 299 | issue = 10 | pages = 105231 | date = October 2023 | pmid = 37690691 | pmc = 10570959 | doi = 10.1016/j.jbc.2023.105231 | doi-access = free }}{{citation | vauthors = Chen X, Li J, Yu L, Dhananjaya D, Maule F, Cook S, Chang L, Gallant J, Press D, Bains JS, Raithatha S, Hagel S, Facchini P | title=Bioproduction platform using a novel cane toad (Rhinella marina) N-methyltransferase for psychedelic-inspired drug discovery | date=10 March 2023 | doi=10.21203/rs.3.rs-2667175/v1 | doi-access=free | url=https://www.researchsquare.com/article/rs-2667175/latest.pdf | access-date=17 March 2025 | page=}} It shows dramatically reduced activity at serotonin receptors compared to tryptamine and mixed effects in terms of psychedelic-like effects in animals.

Pharmacology

2-MT shows affinity (K_i) for the serotonin 5-HT_1A and 5-HT_2A receptors, with K_i values of 1,095{{nbsp}}nM and 7,774{{nbsp}}nM, respectively. These affinities were respectively 34-fold and 3.2-fold lower than those of tryptamine in the same study. It also acts as an agonist of the serotonin 5-HT_1A and 5-HT_2A receptors, with {{Abbrlink|EC₅₀|half-maximal effective concentration}} values of 12,534{{nbsp}}nM and 4,598{{nbsp}}nM, respectively. These activational potencies were respectively 14-fold and 19-fold lower than those of tryptamine in the same study.

It does not produce conditioned place preference (CPP), self-administration, or changes in locomotor activity in rodents. Findings on whether 2-MT produces the head-twitch response (HTR), a behavioral proxy of psychedelic effects, are mixed. In one study, it produced the HTR at a dose of 3{{nbsp}}mg/kg intraperitoneally, and this was completely blocked by the serotonin 5-HT_2A receptor antagonist ketanserin. In another study, both tryptamine and 2-MT did not produce the HTR at a dose of 3{{nbsp}}mg/kg intraperitoneally.

Chemistry

=Derivatives=

A number of derivatives of 2-MT are known, including:{{CiteTiHKAL}}

2,α-Dimethyltryptamine (2,α-DMT or 2-Me-αMT)
2,N,N-Trimethyltryptamine (2,N,N-TMT or 2-Me-DMT)
2-Methyl-N,N-diethyltryptamine (2-Me-DET)
5-Methoxy-2,N,N-trimethyltryptamine (5-MeO-2,N,N-TMT or 2-Me-5-MeO-DMT)

These drugs were synthesized and tested by Alexander Shulgin. He found that the drugs in this group became orally active but generally produced no or only mild psychedelic effects (with the exception of 2-Me-5-MeO-DMT). Instead, they caused effects like tactile enhancement and auditory distortion, among others.

A couple of other derivatives, 2-methyl-5-MeO-DALT and 2-methyl-5-F-DALT, are also known.{{cite journal | vauthors = Klein LM, Cozzi NV, Daley PF, Brandt SD, Halberstadt AL | title = Receptor binding profiles and behavioral pharmacology of ring-substituted N,N-diallyltryptamine analogs | journal = Neuropharmacology | volume = 142 | issue = | pages = 231–239 | date = November 2018 | pmid = 29499272 | pmc = 6230509 | doi = 10.1016/j.neuropharm.2018.02.028 }}

Further derivatives of 2-MT include the following:

2-Methyl-5-HT (a moderately selective serotonin 5-HT₃ receptor full agonist)
2-Methyl-5-chloro-DMT (ST-1936; a selective serotonin 5-HT₆ receptor agonist)
2-Ethyl-5-methoxy-DMT (EMDT; a selective serotonin 5-HT₆ receptor agonist)

EMD-386088 (2-methyl-5-chloro-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole) isn't technically a tryptamine but is very similar and is a serotonin 5-HT₆ receptor partial agonist as well as having moderate affinity for the serotonin 5-HT₃ receptor and acting as a dopamine reuptake inhibitor.

Yet another related compound is 2-HO-NMT, a tryptamine alkaloid.

References

External links

[https://isomerdesign.com/pihkal/explore/7798 2-Methyl-T - Isomer Design]

Category:5-HT1A agonists

Category:5-HT2A agonists

Category:Psychedelic tryptamines