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2,4,5-Trimethoxyamphetamine

From Wikipedia, the free encyclopedia
2,4,5-Trimethoxyamphetamine
Clinical data
Other namesTMA-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 classSerotonergic psychedelic; Hallucinogen
Legal status
Legal status
Pharmacokinetic data
Duration of action8–12 hours[1][2]
Identifiers
  • 1-(2,4,5-trimethoxyphenyl)propan-2-amine
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
Chemical and physical data
FormulaC12H19NO3
Molar mass225.288 g·mol−1
3D model (JSmol)
  • CC(CC1=CC(=C(C=C1OC)OC)OC)N
  • InChI=1S/C12H19NO3/c1-8(13)5-9-6-11(15-3)12(16-4)7-10(9)14-2/h6-8H,5,13H2,1-4H3
  • Key:TVSIMAWGATVNGK-UHFFFAOYSA-N

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

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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

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Pharmacology

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TMA-2 activities
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)
190–1,200 (EC50Tooltip half-maximal effective concentration)
84% (EmaxTooltip maximal efficacy)
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
α2Aα2C >10,000
β1, β2 >10,000
D1D5 >10,000
H1 1,407
H2H4 >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
SERTTooltip Serotonin transporter >10,000 (Ki)
>100,000 (IC50Tooltip half-maximal inhibitory concentration)
>100,000 (EC50) (rat)
NETTooltip Norepinephrine transporter >10,000 (Ki)
>100,000 (IC50)
>100,000 (EC50) (rat)
DATTooltip Dopamine transporter >10,000 (Ki)
>100,000 (IC50)
>100,000 (EC50) (rat)
MAO-ATooltip Monoamine oxidase A >100,000 (IC50) (rat)
MAO-BTooltip Monoamine oxidase 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]

The drug's affinity (Ki) for the serotonin 5-HT2A receptor has been found to be 1,300 nM.[9] Its EC50Tooltip half-maximal effective concentration at the receptor was 190 nM and its EmaxTooltip maximal efficacy 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.[11][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]

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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

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References

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  1. ^ 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.
  2. ^ 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.
  3. ^ a b c https://www.deadiversion.usdoj.gov/schedules/orangebook/c_cs_alpha.pdf
  4. ^ 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.
  5. ^ 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.
  6. ^ "Kᵢ Database". PDSP. 15 March 2025. Retrieved 15 March 2025.
  7. ^ 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.
  8. ^ 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.
  9. ^ 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.
  10. ^ 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.
  11. ^ 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.
  12. ^ 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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