TMA-6 (Ψ-TMA-2) is an example of a Ψ-PEA psychedelic.[1][2][3]
Ψ-Phenethylamines (Ψ-PEA), orpsi-phenethylamines (psi-PEA), also known aspseudo-phenethylamines or as4-substituted 2,6-dimethoxyphenethylamines, are a family ofpsychedelic and related compounds of thephenethylamine family.[1][2][3] They are positionalisomers of the 4-substituted 2,5-dimethoxyphenethylamines (e.g.,2Cs andDOx) and 4-substituted 3,5-dimethoxyphenethylamines (e.g.,scalines and3Cs).[1][2][3]
The Ψ-PEAs are relatively unexplored compared to the other major psychedelic phenethylamine groups.[1][2][3][6][7][8][9] Many Ψ-PEAs have beensynthesized or described, but few are known to have been tested in humans.[1]
^Nichols DE, Glennon RA (1984)."Medicinal Chemistry and Structure-Activity Relationships of Hallucinogens". In Jacobs BL (ed.).Hallucinogens: Neurochemical, Behavioral, and Clinical Perspectives. New York: Raven Press. pp. 95–142.ISBN978-0-89004-990-7.OCLC10324237.The 2,4,6 trisubstitution pattern has received very little attention, but appears quite interesting. The 2,4,6-trimethoxyamphetamine 38 appears to be active in humans in the 30-40 mg range, not too far removed from the potency of 2,4,5-trimethoxyamphetamine (Shulgin and Shulgin, 1991). Further, 2,6-dimethoxy-4-methylamphetamine (39), a positional isomer of DOM, has been reported to be active in humans in the 15-25 mg range (Shulgin and Shulgin, 1991). Based on the known structure-activity relationships in the 2,4,5-substituted series, one might anticipate that more hydrophobic 4 substituents in this series would lead to quite active compounds. However, no additional members of the series have been reported, nor have any animal or biochemical pharmacological studies been carried out to indicate whether the mechanism of action of the 2,4,6-substituted series is similar to that of compounds with the other substituent orientations.
^Jacob P, Shulgin AT (1994)."Structure-activity relationships of the classic hallucinogens and their analogs"(PDF).NIDA Research Monograph.146:74–91.PMID8742795.The second group has a 2,4,6-substitution pattern. The majority of the compounds listed in the last few tables has carried the 3,4,5- or the 2,4,5-substitution pattern. The similarity of potency between TMA-2 and TMA-6 (the latter with the 2,4,6 substitution pattern, see table 5) has opened up a new family of hallucinogenic amphetamines, one of the authors' current areas of research. With this group also, the 4-position appears to dictate the potency and nature of response. It seems that each of the 2,4,5-substituted materials may have an active 2,4,6-counterpart. The isomer that corresponds to DOM (2,6-dimethoxy-4-methylamphetamine [pseudo-DOM]) is active at 15 to 25 mg orally. Synthetic procedures are now in hand to prepare the pseudo analogs of the 2C-T family with various alkylthio groups at the 4-position.
^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.ISBN978-0-12-433951-4.This review to date has considered the relatives of the 3,4,5-trisubstitution ring pattern (modest activity) and the considerably more potent 2,4,5-trisubstitution pattern. As was noted in the comments comparing TMA-2 with TMA-6, the 2,4,6-orientation bids fair to be every bit as important as the 2,4,5-system, although it has as yet been almost unexplored, either chemically or pharmacologically. A nomenclature that has been used to refer to this branch which is parallel to the 2,4,5-group, is to use the code name of the drug and precede it with the Greek letter psi. This was introduced above with the compound Ψ-2C-T-4. Thus, the lead drug of this section (DOM or 2,5-dimethoxy-4-methylamphetamine) becomes Ψ-DOM (2,6-dimethoxy-4-methylamphetamine). Clinical studies have shown it to be active as a hallucinogen in the 15—25mg range, with a mescaline equivalency of 15. There is too little data at the present time to determine any quantitative relationship between the 2,4,5-normal series and the but it appears quite possible that the two parallel families are, at least as to their quantitative properties, quite similar.
^abKolaczynska, K. E., Trachsel, D., Hoener, M. C., Liechti, M. E., & Luethi, D. (2025). Receptor interaction profiles of 4-alkoxy-2, 6-dimethoxyphenethylamines (Ψ derivatives) and related amphetamines. Frontiers in Pharmacology, 16, 1703480.https://doi.org/10.3389/fphar.2025.1703480
