^abcShulgin AT (2003)."Basic Pharmacology and Effects". In Laing RR (ed.).Hallucinogens: A Forensic Drug Handbook. Forensic Drug Handbook Series. Elsevier Science. pp. 67–137.ISBN978-0-12-433951-4. Retrieved1 February 2025.Quite a different story follows the inclusion of a methyl group at the indolic 2-position, in both of the two above groups. With the aryl, N-substituted analogues or DMT, three compounds are of specific interest. These are the three 2-methyl homologues or DMT, 5-MeO-DMT and DET. The first of these, 2,N,N-trimethyltryptamine (2,N,N-TMT) is orally active in the 50 to 100mg range. This is a potency very similar to the prototype DMT, but with this compound there is oral activity. It is as if just the presence of some aliphatic entity in the space between the indole ring and the 3-side-chain, whether it is an alpha-methyl or a 2-methyl, effectively protects the molecule from the monoamine oxidase. A similar protection from oxidative deamination, although at a considerable drop in potency, is seen with the 2-methylation of 5-methoxy-N,N-dimethyltryptamine. This base, 5-MeO-2,N,N-TMT, is orally active in the dose range of 75–150mg, down by a factor of 10 from the 5-MeO-DMT parent. The corresponding homologue of DET is 2-Me-DET. It is orally active with doses in the 80 to 120mg range. One example of a 2-methylated-alpha-methyltryptamine has been studied in humans. This is 2,alpha-dimethyltryptamine, or 2,α-DMT. It leads to a gentle, pleasurable intoxication with oral doses in the mg range.
^abDuan W, Cao D, Wang S, Cheng J (January 2024)."Serotonin 2A Receptor (5-HT2AR) Agonists: Psychedelics and Non-Hallucinogenic Analogues as Emerging Antidepressants".Chem Rev.124 (1):124–163.doi:10.1021/acs.chemrev.3c00375.PMID38033123.Compared to 5-MeO-DMT (6), compounds with 2-position substituents displayed conserved affinity at the 5-HT6 receptor but not at the 5-HT2AR.138 For example, the methyl- (17, r5- HT2AR Ki > 10,000 nM), ethyl- (18, r5-HT2AR Ki > 10,000 nM), and phenyl- (19, r5-HT2AR Ki > 470 nM) substitutions totally abolished binding affinity for the 5-HT2AR (Figure 5B).138 [...] (138) Glennon, R. A.; Lee, M.; Rangisetty, J. B.; Dukat, M.; Roth, B. L.; Savage, J. E.; McBride, A.; Rauser, L.; Hufeisen, S.; Lee, D. K. H. 2-Substituted Tryptamines: Agents with Selectivity for 5-HT6 Serotonin Receptors. J. Med. Chem. 2000, 43, 1011−1018.
^abcdeGlennon RA, Lee M, Rangisetty JB, Dukat M, Roth BL, Savage JE, McBride A, Rauser L, Hufeisen S, Lee DK (March 2000). "2-Substituted tryptamines: agents with selectivity for 5-HT(6) serotonin receptors".J Med Chem.43 (5):1011–1018.doi:10.1021/jm990550b.PMID10715164.
^"Kᵢ Database".PDSP. 26 March 2025. Retrieved26 March 2025.
