Methyl-TMA

Methyl-TMA
Clinical data
Other namesMETHYL-TMA; N-Me-TMA; N-Methyl-TMA; α,N-Dimethylmescaline; N-Methyl-3,4,5-trimethoxyamphetamine
Routes of
administration		Oral
Drug classSerotonergic psychedelic; Hallucinogen
ATC code
  • None
Identifiers
  • N-methyl-1-(3,4,5-trimethoxyphenyl)propan-2-amine
CAS Number
PubChem CID
ChemSpider
Chemical and physical data
FormulaC13H21NO3
Molar mass239.315 g·mol−1
3D model (JSmol)
  • CC(CC1=CC(=C(C(=C1)OC)OC)OC)NC
  • InChI=1S/C13H21NO3/c1-9(14-2)6-10-7-11(15-3)13(17-5)12(8-10)16-4/h7-9,14H,6H2,1-5H3
  • Key:XYKHBBWJSFSLRF-UHFFFAOYSA-N

Methyl-TMA, or N-methyl-TMA, also known as N-methyl-3,4,5-trimethoxyamphetamine, is a psychedelic drug of the phenethylamine, amphetamine, and 3C families. It is the N-methyl derivative of 3,4,5-trimethoxyamphetamine (TMA) as well as the α,N-dimethyl derivative of mescaline (3,4,5-trimethoxyphenethylamine).

Use and effects

N-Methylation of psychedelic phenethylamines has invariably greatly reduced or eliminated their hallucinogenic activity. Examples of this include related compounds like Beatrice (N-methyl-DOM) and methyl-DOB (N-methyl-DOB), which at assessed doses appear to be inactive as psychedelics in humans. According to Alexander Shulgin in his book PiHKAL (Phenethylamines I Have Known and Loved) however, methyl-TMA showed "some mental disturbances" at the highest assessed dose of 240 mg orally. For comparison, the active dose range of TMA is 100 to 250 mg orally.

Interactions

History

Methyl-TMA was first described in the scientific literature by at least 1984. It was subsequently described further by Shulgin in PiHKAL in 1991.

Society and culture

Canada

Methyl-TMA is a controlled substance in Canada under phenethylamine blanket-ban language.

See also

References

  1. 1 2 3 4 5 6 7 8 Shulgin A, Shulgin A (September 1991). PiHKAL: A Chemical Love Story. Berkeley, California: Transform Press. ISBN 0-9630096-0-5. OCLC 25627628. "Three additional N-methylated homologues of known psychedelics warrant mention, but do not really deserve separate recipes. This is because they have had only the most cursory assaying, which I have learned about by personal correspondence. [...] METHYL-TMA [...] had been run up in several trials to a maximum of 240 [mg], with some mental disturbances mentioned only at this highest level. METHYL-TMA-2 [...] had been tried at up to 120 [mg] without any effects. METHYL-TMA-6 [...] had been tried at up to 30 [mg] and it, too, was apparently without effects. These are reports that I have heard from others, but I have had no personal experience with them. Those that I can describe from personal experience are entered separately as recipes of their own. And there are many, many other N-methyl homologues which have been prepared and characterized in the literature, and have yet to be tasted. So far, however, the only consistent thing seen is that, with N-methylation, the potency of the psychedelics is decreased, but the potency of the stimulants appears to be pretty much maintained."
  2. 1 2 3 Shulgin A, Manning T, Daley P (2011). The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds. Vol. 1. Berkeley: Transform Press. pp. 288, 350, 383, 408. ISBN 978-0-9630096-3-0.
  3. ↑ Nichols DE (2018). Chemistry and Structure-Activity Relationships of Psychedelics. Current Topics in Behavioral Neurosciences. Vol. 36. pp. 1–43. doi:10.1007/7854_2017_475. ISBN 978-3-662-55878-2. PMID 28401524. Although the most active tryptamine hallucinogens are N,N-dialkylated, the phenethylamines generally cannot tolerate even a single N-substitution. Even small groups such as methyl or ethyl (see Table 2) abolish their hallucinogenic activity.
  4. 1 2 Shulgin AT (1980). "Hallucinogens". In Burger A, Wolf ME (eds.). Burger's Medicinal Chemistry. Vol. 3 (4 ed.). New York: Wiley. pp. 1109–1137. ISBN 978-0-471-01572-7. OCLC 219960627. Of all the variously substituted phenylisopropylamines that have been N-methylated and titrated in man (including the homologs of TMA-2, 2,5-DMA, DOM, and DOB: 60.22b, 60.22i, 60.22aa, and 60.22ff, respectively), it is only the methylenedioxy compound 60.23a that has maintained quantitative potency (94). As with mescaline itself, dimethylation of this compound eliminates any central action.
  5. 1 2 Jacob P, Shulgin AT (1994). "Structure-Activity Relationships of the Classic Hallucinogens and Their Analogs". In Lin GC, Glennon RA (eds.). Hallucinogens: An Update (PDF). National Institute on Drug Abuse Research Monograph Series. Vol. 146. National Institute on Drug Abuse. pp. 74–91. PMID 8742795. Archived from the original on 13 July 2025. [MDA] is also remarkable because the N-methyl homolog 3,4 (MDMA) has biological activity, although the nature of its action places it outside of this review. No other phenethylamine hallucinogen retains central activity on N-methylation.
  6. ↑ Trachsel D, Lehmann D, Enzensperger C (2013). Phenethylamine: von der Struktur zur Funktion [Phenethylamines: From Structure to Function]. Nachtschatten-Science (in German) (1 ed.). Solothurn: Nachtschatten-Verlag. pp. 834–835, 878. ISBN 978-3-03788-700-4. OCLC 858805226. 8.5.26. N-Substitution von 2,4,5-trisubstituierten Phenylalkylaminen: Einerseits wurde der Einfluss von N-Alkyl-, andererseits derjenige von N-Heterogruppen-Substituenten geprüft. Allgemein ist bekannt, dass das Einführen von Alkylsubstituenten am Stickstoff von psychedelischen Phenylalkylaminen eine Abnahme der HT2-Rezeptoraffinitäten zur Folge hat [29, 150, 151]. Die Wirkungsabschwächung konnte mit den potenten Substanzen DOB (2) und DOM (8) im Menschen bestätigt werden [8]: N-Methyl-DOM (316; BEATRICE) und METHYL-DOB (317) erwiesen sich im Vergleich zu den beiden unmethylierten Verbindungen als massiv weniger aktiv; die aktive Dosis wurde dabei noch nicht eruiert. METHYL-DOET (318; DOETM) erwies sich bei einer Dosierung von 18mg bereits als deutlich aktiv [140]; die Wirkungen wurden im Vergleich zu DOET (14) als ruhiger und angenehmer beschrieben. [...] 318; METHYL-DOET, 18mg, 8-10h. [...] [140] P. Rausch. Persönliche Mitteilung, 2009.
  7. ↑ Clark C (1 October 1984). "The Identification of Methoxy-N-Methylamphetamines". Journal of Forensic Sciences. 29 (4): 1056–1071. doi:10.1520/JFS11772J. ISSN 0022-1198.
  8. ↑ "Controlled Drugs and Substances Act". Department of Justice Canada. Retrieved 19 January 2026.