2,4,5-Trimethoxyamphetamine
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| Clinical data | |
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| Other names | TMA-2; 2,4,5-TMA; 2,4,5-Trimethoxy-α-methylphenethylamine; 2,5-Dimethoxy-4-methoxyamphetamine; 4-Methoxy-2,5-dimethoxyamphetamine; DOMeO; DOOMe; DOO |
| Routes of administration | Oral[1][2] |
| Drug class | Serotonergic psychedelic; Hallucinogen |
| Legal status | |
| Legal status | |
| Pharmacokinetic data | |
| Duration of action | 8–12 hours[1][2] |
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| CAS Number | |
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| Chemical and physical data | |
| Formula | C12H19NO3 |
| Molar mass | 225.288 g·mol−1 |
| 3D model (JSmol) | |
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2,4,5-Trimethoxyamphetamine (2,4,5-TMA), also known as TMA-2 or as 2,5-dimethoxy-4-methoxyamphetamine (DOMeO), 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 also notable in being the 4-methoxylated member of the DOx (i.e., 4-substituted-2,5-dimethoxyamphetamine) series of drugs.[1][2]
Use and effects
TMA-2 is a serotonergic psychedelic and produces hallucinogenic effects.[1][2] It is said to be active at doses of 20 to 40 mg and to have a duration of 8 to 12 hours.[1] It is much more potent than its positional isomer 3,4,5-trimethoxyamphetamine (3,4,5-TMA, TMA, or TMA-1), which is said to be active at doses of 100 to 250 mg and to have a duration of 6 to 8 hours.[4] However, DOM (2,5-dimethoxy-4-methylamphetamine), the analogue of TMA-2 in which its 4-methoxy group has been replaced with a more lipophilic 4-methyl group, is about 10 times more potent than TMA-2.[5]
Interactions
Pharmacology
| Target | Affinity (Ki, nM) |
|---|---|
| 5-HT1A | >10,000 |
| 5-HT1B | >10,000 |
| 5-HT1D | >10,000 |
| 5-HT1E | >10,000 |
| 5-HT1F | ND |
| 5-HT2A | 57.9–1,300 (Ki) 190–1,860 (EC50) 84–102% (Emax) |
| 5-HT2B | 154–307 (Ki) 270 (EC50) 78% (Emax) |
| 5-HT2C | 87.7–5,300 |
| 5-HT3 | >10,000 |
| 5-HT4 | ND |
| 5-HT5A | >10,000 |
| 5-HT6 | >10,000 |
| 5-HT7 | >10,000 |
| α1A, α1B | >10,000 |
| α1D | ND |
| α2A–α2C | >10,000 |
| β1, β2 | >10,000 |
| D1–D5 | >10,000 |
| H1 | 1,407 |
| H2–H4 | >10,000 |
| M1, M3, M4 | ND |
| M2, M5 | >10,000 |
| TAAR1 | >4,400 (Ki) (mouse) 3,100 (Ki) (rat) ND (EC50) (human) |
| I1 | ND |
| σ1, σ2 | ND |
| SERT | >10,000 (Ki) >100,000 (IC50) >100,000 (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 | >100,000 (IC50) (rat) |
| MAO-B | >100,000 (IC50) (rat) |
| Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs: [6][7][8][9][10][11][12][13] | |
The drug's affinity (Ki) for the serotonin 5-HT2A receptor has been found to be 1,300 nM.[9] Its EC50 at the receptor was 190 nM and its Emax was 84%.[9] The drug was also active at the serotonin 5-HT2B receptor and, to a much lesser extent, at the serotonin 5-HT2C receptor.[9] TMA-2 is inactive at the monoamine transporters.[12][9] It was inactive at the mouse trace amine-associated receptor 1 (TAAR1), whereas it bound to the rat TAAR1 with an affinity (Ki) of 3,100 nM and was not assessed at the human TAAR1.[9]
Legal status
As of 2011, TMA-2 is not an explicitly controlled substance in the United States.[2][3] However, it is a positional isomer of 3,4,5-trimethoxyamphetamine (TMA), and thus is a Schedule I controlled substance in states in which isomers are controlled substances.[2][3]
See also
- 2,4,5-Trimethoxyphenethylamine (2C-O)
- 2,5-Dimethoxyamphetamine (2,5-DMA, DMA-4, or DOH)
References
- ^ a b c d e f g 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.
- ^ a b c d e f g h i Shulgin A, Manning T, Daley PF (2011). "#118. TMA-2". The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds. Vol. 1. Berkeley: Transform Press. ISBN 978-0-9630096-3-0.
- ^ a b c https://www.deadiversion.usdoj.gov/schedules/orangebook/c_cs_alpha.pdf
- ^ 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.
- ^ Nichols, David E. (2012). "Structure–activity relationships of serotonin 5-HT2A agonists". Wiley Interdisciplinary Reviews: Membrane Transport and Signaling. 1 (5): 559–579. doi:10.1002/wmts.42. ISSN 2190-460X.
- ^ "Kᵢ Database". PDSP. 15 March 2025. Retrieved 15 March 2025.
- ^ Liu, Tiqing. "BDBM50005253 (+/-)1-Methyl-2-(2,4,5-trimethoxy-phenyl)-ethylamine::1-(2,4,5-trimethoxyphenyl)propan-2-amine::1-Methyl-2-(2,4,5-trimethoxy-phenyl)-ethylamine::1-Methyl-2-(2,4,5-trimethoxy-phenyl)-ethylamine(2,4,5-TMA)::CHEMBL8389". 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 f Kolaczynska KE, Luethi D, Trachsel D, Hoener MC, Liechti ME (2019). "Receptor Interaction Profiles of 4-Alkoxy-Substituted 2,5-Dimethoxyphenethylamines and Related Amphetamines". Front Pharmacol. 10: 1423. doi:10.3389/fphar.2019.01423. PMC 6893898. PMID 31849671.
- ^ Nelson DL, Lucaites VL, Wainscott DB, Glennon RA (January 1999). "Comparisons of hallucinogenic phenylisopropylamine binding affinities at cloned human 5-HT2A, -HT(2B) and 5-HT2C receptors". Naunyn Schmiedebergs Arch Pharmacol. 359 (1): 1–6. doi:10.1007/pl00005315. PMID 9933142.
- ^ Flanagan TW, Billac GB, Landry AN, Sebastian MN, Cormier SA, Nichols CD (April 2021). "Structure-Activity Relationship Analysis of Psychedelics in a Rat Model of Asthma Reveals the Anti-Inflammatory Pharmacophore". ACS Pharmacol Transl Sci. 4 (2): 488–502. doi:10.1021/acsptsci.0c00063. PMC 8033619. PMID 33860179.
- ^ a b Nagai F, Nonaka R, Satoh Hisashi Kamimura K (March 2007). "The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain". Eur J Pharmacol. 559 (2–3): 132–137. doi:10.1016/j.ejphar.2006.11.075. PMID 17223101.
- ^ 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.
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