3,4,5-Trimethoxyamphetamine
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| Other names | Trimethoxyamphetamine; TMA; TMA-1; 3,4,5-TMA; α-Methylmescaline; alpha-Methylmescaline; AMM; Mescalamphetamine; 3,4,5-Trimethoxy-α-methylphenethylamine |
| Routes of administration | Oral[1][2] |
| Drug class | Serotonergic psychedelic; Hallucinogen; Serotonin 5-HT2A receptor agonist |
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| Pharmacokinetic data | |
| Duration of action | 6–8 hours[1][2] |
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| Chemical and physical data | |
| Formula | C12H19NO3 |
| Molar mass | 225.288 g·mol−1 |
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Trimethoxyamphetamine (TMA or TMA-1), also known as 3,4,5-trimethoxyamphetamine (3,4,5-TMA), α-methylmescaline, or mescalamphetamine, is a psychedelic drug of the phenethylamine and amphetamine families.[1][2] It is one of the trimethoxyamphetamine (TMA) series of positional isomers.[1][2] The drug is notable in being the amphetamine (i.e., α-methylated) analogue of mescaline (3,4,5-trimethoxyphenethylamine).[1][2]
Use and effects
[edit]TMA is a serotonergic psychedelic and produces hallucinogenic effects.[1][2] It is said to be active at doses of 100 to 250 mg and to have a duration of 6 to 8 hours.[1][4] For comparison, mescaline is typically used at doses of 200 to 500 mg and is said to have a duration of 10 to 12 hours or longer.[5] TMA's positional isomer 2,4,5-trimethoxyamphetamine (2,4,5-TMA or TMA-2) is much more potent than TMA, with a dosage of 20 to 40 mg and a duration of 8 to 12 hours.[6]
Interactions
[edit]Pharmacology
[edit]| Target | Affinity (Ki, nM) |
|---|---|
| 5-HT1A | 1,678–>5,600 |
| 5-HT1B | 2,855 |
| 5-HT1D | 3,035 |
| 5-HT1E | 3,369 |
| 5-HT1F | ND |
| 5-HT2A | >10,000 (Ki) 41.3–1,700 (EC50) 40–96% (Emax) |
| 5-HT2B | 477 (Ki) >10,000 (EC50) |
| 5-HT2C | 4,600–>10,000 (Ki) 47.4 (EC50) 92% (Emax) |
| 5-HT3 | >10,000 |
| 5-HT4 | ND |
| 5-HT5A | >10,000 |
| 5-HT6 | >10,000 |
| 5-HT7 | 749 |
| α1A, α1B | >10,000 |
| α1D | ND |
| α2A | 2,071–4,030 |
| α2B | >10,000 |
| α2C | 5,014 |
| β1, β2 | >10,000 |
| D1–D5 | >10,000 |
| H1–H4 | >10,000 |
| M1, M3, M4 | ND |
| M2, M5 | >10,000 |
| nACh | 260–>10,000 |
| TAAR1 | 1,800 (Ki) (mouse) 3,200 (Ki) (rat) >10,000 (EC50) (human) |
| I1 | >10,000 |
| σ1 | 537 |
| σ2 | 537 |
| SERT | >10,000 (Ki) >100,000 (IC50) 16,000 (EC50) (rat) |
| NET | >10,000 (Ki) >100,000 (IC50) >100,000 (EC50) (rat) |
| DAT | >10,000 (Ki) >100,000 (IC50) >100,000 (EC50) (rat) |
| MAO-A | >200,000 (IC50) |
| MAO-B | >200,000 (IC50) |
| Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs: [7][8][9][10][11][12][13][14] | |
TMA is a low-potency serotonin 5-HT2A receptor partial agonist, with an affinity (Ki) of >12,000 nM, an EC50 of 1,700 nM, and an Emax of 40%.[10] Conversely, it was inactive at the serotonin 5-HT1A, 5-HT2B and 5-HT2C receptors and at several other receptors, at least at the assessed concentrations (up to 10,000 nM).[10] It showed affinity for the mouse and rat trace amine-associated receptor 1 (TAAR1) (Ki = 1,800 nM and 3,200 nM, respectively), whereas it was inactive at the human TAAR1 (EC50 > 10,000 nM).[10]
TMA is also a very low-potency serotonin releasing agent (SRA), with an EC50 value of 16,000 nM.[11] In contrast, it is inactive as a releasing agent and reuptake inhibitor of dopamine and norepinephrine (EC50 > 100,000 nM).[11] Despite its apparent SRA activity in vitro, TMA did not increase brain serotonin or dopamine levels in rodents in vivo.[14] TMA is similarly inactive as a monoamine oxidase inhibitor (MAOI), including of both monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B) (IC50 > 200,000 nM).[13][14]
The low potency of TMA as a serotonin 5-HT2A receptor agonist is analogous to the case of mescaline, which is a well-known and widely used psychedelic but is likewise a very low-potency agonist of this receptor, showing an affinity (Ki) of 9,400 nM, an EC50 of 10,000 nM, and an Emax of 56% in the same study.[10] For comparison, DOM has shown an affinity (Ki) of 88 nM and an EC50 of 4 to 24 nM.[15]
Legal status
[edit]TMA is a Schedule I controlled substance in the United States.[2][3]
See also
[edit]- α-Ethylmescaline (3,4,5-trimethoxy-α-ethylphenethylamine)
- 3,4-Dimethoxyamphetamine (3,4-DMA)
References
[edit]- ^ a b c d e f g Shulgin AT, Shulgin A (1991). "#157 TMA 3,4,5-TRIMETHOXYAMPHETAMINE". PiHKAL: A Chemical Love Story (1st ed.). Berkeley, CA: Transform Press. ISBN 9780963009609. OCLC 25627628.
- ^ a b c d e f g h Shulgin A, Manning T, Daley PF (2011). "#117. TMA". The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds. Vol. 1. Berkeley: Transform Press. ISBN 978-0-9630096-3-0.
- ^ a b https://www.deadiversion.usdoj.gov/schedules/orangebook/c_cs_alpha.pdf
- ^ Halberstadt AL, Luethi D, Hoener MC, Trachsel D, Brandt SD, Liechti ME (January 2023). "Use of the head-twitch response to investigate the structure-activity relationships of 4-thio-substituted 2,5-dimethoxyphenylalkylamines". Psychopharmacology. 240 (1). Berlin: 115–126. doi:10.1007/s00213-022-06279-2. PMC 9816194. PMID 36477925.
For example, 3,4,5-trimethoxyamphetamine (TMA) is active at a dose range of 100–250 mg, whereas its 2,4,5-regioisomer (2,4,5-trimethoxyamphetamine, TMA-2) is active at 20–40 mg (Shulgin and Shulgin 1991).
- ^ Vamvakopoulou IA, Narine KA, Campbell I, Dyck JR, Nutt DJ (January 2023). "Mescaline: The forgotten psychedelic". Neuropharmacology. 222: 109294. doi:10.1016/j.neuropharm.2022.109294. PMID 36252614.
- ^ Shulgin AT, Shulgin A (1991). "#158 TMA-2 2,4,5-TRIMETHOXYAMPHETAMINE". PiHKAL: A Chemical Love Story (1st ed.). Berkeley, CA: Transform Press. ISBN 9780963009609. OCLC 25627628.
- ^ "PDSP Database". UNC (in Zulu). Retrieved 15 March 2025.
- ^ Liu T. "BDBM50005256 (+/-)1-Methyl-2-(3,4,5-trimethoxy-phenyl)-ethylamine::1-Methyl-2-(3,4,5-trimethoxy-phenyl)-ethylamine::CHEMBL30336::TMA". BindingDB. Retrieved 14 March 2025.
- ^ Ray TS (February 2010). "Psychedelics and the human receptorome". PLOS ONE. 5 (2): e9019. Bibcode:2010PLoSO...5.9019R. doi:10.1371/journal.pone.0009019. PMC 2814854. PMID 20126400.
- ^ a b c d e Kolaczynska KE, Luethi D, Trachsel D, Hoener MC, Liechti ME (2021). "Receptor Interaction Profiles of 4-Alkoxy-3,5-Dimethoxy-Phenethylamines (Mescaline Derivatives) and Related Amphetamines". Frontiers in Pharmacology. 12: 794254. doi:10.3389/fphar.2021.794254. PMC 8865417. PMID 35222010.
- ^ a b c Nagai F, Nonaka R, Satoh Hisashi Kamimura K (March 2007). "The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain". European Journal of Pharmacology. 559 (2–3): 132–137. doi:10.1016/j.ejphar.2006.11.075. PMID 17223101.
- ^ Whiteaker P, Sharples CG, Wonnacott S (May 1998). "Agonist-induced up-regulation of alpha4beta2 nicotinic acetylcholine receptors in M10 cells: pharmacological and spatial definition". Mol Pharmacol. 53 (5): 950–962. doi:10.1016/S0026-895X(24)13263-4. PMID 9584223.
- ^ a b Reyes-Parada M, Iturriaga-Vasquez P, Cassels BK (2019). "Amphetamine Derivatives as Monoamine Oxidase Inhibitors". Frontiers in Pharmacology. 10: 1590. doi:10.3389/fphar.2019.01590. PMC 6989591. PMID 32038257.
- ^ a b c Matsumoto T, Maeno Y, Kato H, Seko-Nakamura Y, Monma-Ohtaki J, Ishiba A, et al. (August 2014). "5-hydroxytryptamine- and dopamine-releasing effects of ring-substituted amphetamines on rat brain: a comparative study using in vivo microdialysis". European Neuropsychopharmacology. 24 (8): 1362–1370. doi:10.1016/j.euroneuro.2014.04.009. PMID 24862256.
- ^ Luethi D, Rudin D, Hoener MC, Liechti ME (2022). "Monoamine Receptor and Transporter Interaction Profiles of 4-Alkyl-Substituted 2,5-Dimethoxyamphetamines". The FASEB Journal. 36 (S1). doi:10.1096/fasebj.2022.36.S1.R2691. ISSN 0892-6638.