Chemistry:2-Methyltryptamine

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2-Methyltryptamine (2-MT, 2-Me-T, or 2-methyl-T) is a serotonin receptor agonist of the tryptamine family.[1][2][3] It shows dramatically reduced activity at serotonin receptors compared to tryptamine[2][3] and mixed effects in terms of psychedelic-like effects in animals.[1][3]

Pharmacology

Pharmacodynamics

2-MT shows affinity (Ki) for the serotonin 5-HT1A and 5-HT2A receptors, with Ki values of 1,095 nM and 7,774 nM, respectively.[2][3] These affinities were respectively 34-fold and 3.2-fold lower than those of tryptamine in the same study.[2][3] It also acts as an agonist of the serotonin 5-HT1A and 5-HT2A receptors, with EC50 values of 12,534 nM and 4,598 nM, respectively.[3] These activational potencies were respectively 14-fold and 19-fold lower than those of tryptamine in the same study.[3]

It does not produce conditioned place preference (CPP), self-administration, or changes in locomotor activity in rodents.[1] Findings on whether 2-MT produces the head-twitch response (HTR), a behavioral proxy of psychedelic effects, are mixed.[1][3] In one study, it produced the HTR at a dose of 3 mg/kg intraperitoneally, and this was completely blocked by the serotonin 5-HT2A receptor antagonist ketanserin.[1] In another study, both tryptamine and 2-MT did not produce the HTR at a dose of 3 mg/kg intraperitoneally.[3]

Chemistry

Derivatives

A number of derivatives of 2-MT are known, including:[4]

  • 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.[4] 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).[4] Instead, they caused effects like tactile enhancement and auditory distortion, among others.[4]

A few other derivatives, including 2-methyl-DiPT, 2-methyl-iPALT, 2-methyl-5-MeO-DALT, and 2-methyl-5-F-DALT, are also known.[4][5][6]

Further derivatives of 2-MT include the following:

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.

See also

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 "Four Novel Synthetic Tryptamine Analogs Induce Head-Twitch Responses and Increase 5-HTR2a in the Prefrontal Cortex in Mice". Biomolecules & Therapeutics 28 (1): 83–91. January 2020. doi:10.4062/biomolther.2019.049. PMID 31230432. 
  2. ↑ 2.0 2.1 2.2 2.3 "A cane toad (Rhinella marina) N-methyltransferase converts primary indolethylamines to tertiary psychedelic amines". The Journal of Biological Chemistry 299 (10). October 2023. doi:10.1016/j.jbc.2023.105231. PMID 37690691. 
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 3.8 Bioproduction platform using a novel cane toad (Rhinella marina) N-methyltransferase for psychedelic-inspired drug discovery, 10 March 2023, doi:10.21203/rs.3.rs-2667175/v1, https://www.researchsquare.com/article/rs-2667175/latest.pdf, retrieved 17 March 2025 
  4. ↑ 4.0 4.1 4.2 4.3 4.4 Shulgin, Alexander; Shulgin, Ann (September 1997). TiHKAL: The Continuation. Berkeley, California: Transform Press. ISBN 0-9630096-9-9. OCLC 38503252. http://www.erowid.org/library/books_online/tihkal/tihkal.shtml. 
  5. ↑ "Receptor binding profiles and behavioral pharmacology of ring-substituted N,N-diallyltryptamine analogs". Neuropharmacology 142: 231–239. November 2018. doi:10.1016/j.neuropharm.2018.02.028. PMID 29499272. 
  6. ↑ Daley PF, Cozzi NV, Callaway WB, "Asymmetric allyl tryptamines", US patent 20240277665A1, issued 4 March 2024, assigned to Alexander Shulgin Research Institute Inc.



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