2,4,5-Trimethoxyamphetamine

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]

TMA-2

Clinical data
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	US: Schedule I[2][3]
Pharmacokinetic data
Duration of action	8–12 hours[1][2]
Identifiers
IUPAC name 1-(2,4,5-trimethoxyphenyl)propan-2-amine
CAS Number	1083-09-6
PubChem CID	31014
ChemSpider	28773
UNII	713Z3SL0TJ
KEGG	C22746
ChEMBL	ChEMBL8389
Chemical and physical data
Formula	C12H19NO3
Molar mass	225.288 g·mol−1
3D model (JSmol)	Interactive image
SMILES CC(CC1=CC(=C(C=C1OC)OC)OC)N
InChI 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

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][4] 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.^[5] 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.^[6]

Interactions

See also: Psychedelic drug § Interactions, and Trip killer § Serotonergic psychedelic antidotes

Pharmacology

Pharmacodynamics

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) 190–1,860 (EC50Tooltip half-maximal effective concentration) 84–102% (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
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
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: [7][8][9][10][11][12][13][14][15]

TMA-2's affinity (K_i) for the serotonin 5-HT_2A receptor has been found to be 1,300 nM.^[10] Its EC₅₀Tooltip half-maximal effective concentration at the receptor was 190 nM and its E_maxTooltip maximal efficacy was 84%.^[10] The drug was also active at the serotonin 5-HT_2B receptor and, to a much lesser extent, at the serotonin 5-HT_2C receptor.^[10] In an earlier study, its affinities (K_i) were 1,650 nM at the serotonin 5-HT₂ receptor and 46,400 nM at the serotonin 5-HT₁ receptor.^[16][17] TMA-2 is inactive at the monoamine transporters.^[14][10] It was inactive at the mouse trace amine-associated receptor 1 (TAAR1), whereas it bound to the rat TAAR1 with an affinity (K_i) of 3,100 nM and was not assessed at the human TAAR1.^[10]

Chemistry

Derivatives

See also: 2,5-Dimethoxy-4-ethoxyamphetamine § Derivatives

A variety of derivatives of TMA-2 have been developed and studied.^[10][18]

History

TMA-2 was first described in the scientific literature by Bruckner in 1933.^[19][2][20] Subsequently, Alexander Shulgin first described the hallucinogenic effects of TMA-2 in 1964.^{[19][21][22][2]}

Society and culture

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

• Substituted methoxyphenethylamine
• 2,4,5-Trimethoxyphenethylamine (2C-O)
• 2,5-Dimethoxyamphetamine (2,5-DMA, DMA-4, or DOH)