# 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. It is one of the trimethoxyamphetamine (TMA) series of positional isomers. The drug is also notable in being the 4-methoxylated member of the DOx (i.e., 4-substituted-2,5-dimethoxyamphetamine) series of drugs.

## Use and effects

TMA-2 is a serotonergic psychedelic and produces hallucinogenic effects. It is said to be active at doses of 20 to 40 mg and to have a duration of 8 to 12 hours. 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. 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.

## Pharmacology

TMA-2 activities :
| Target | Affinity (K$_i$, nM) |
| 5-HT$_{1A}$ | >10,000 |
| 5-HT$_{1B}$ | >10,000 |
| 5-HT$_{1D}$ | >10,000 |
| 5-HT$_{1E}$ | >10,000 |
| 5-HT$_{1F}$ | ND |
| 5-HT$_{2A}$ | 57.9–1,300 (K$_i$) 190–1,860 (EC$_{50}$Tooltip half-maximal effective concentration) 84–102% (E$_{max}$Tooltip maximal efficacy) |
| 5-HT$_{2B}$ | 154–307 (K$_i$) 270 (EC$_{50}$) 78% (E$_{max}$) |
| 5-HT$_{2C}$ | 87.7–5,300 |
| 5-HT$_3$ | >10,000 |
| 5-HT$_4$ | ND |
| 5-HT$_{5A}$ | >10,000 |
| 5-HT$_6$ | >10,000 |
| 5-HT$_7$ | >10,000 |
| α$_{1A}$, α$_{1B}$ | >10,000 |
| α$_{1D}$ | ND |
| α$_{2A}$–α$_{2C}$ | >10,000 |
| β$_1$, β$_2$ | >10,000 |
| D$_1$–D$_5$ | >10,000 |
| H$_1$ | 1,407 |
| H$_2$–H$_4$ | >10,000 |
| M$_1$, M$_3$, M$_4$ | ND |
| M$_2$, M$_5$ | >10,000 |
| TAAR$_1$ | >4,400 (K$_i$) (mouse) 3,100 (K$_i$) (rat) ND (EC$_{50}$) (human) |
| I$_1$ | ND |
| σ$_1$, σ$_2$ | ND |
| SERTTooltip Serotonin transporter | >10,000 (K$_i$) >100,000 (IC$_{50}$Tooltip half-maximal inhibitory concentration) >100,000 (EC$_{50}$) (rat) |
| NETTooltip Norepinephrine transporter | >10,000 (K$_i$) >100,000 (IC$_{50}$) >100,000 (EC$_{50}$) (rat) |
| DATTooltip Dopamine transporter | >10,000 (K$_i$) >100,000 (IC$_{50}$) >100,000 (EC$_{50}$) (rat) |
| MAO-ATooltip Monoamine oxidase A | >100,000 (IC$_{50}$) (rat) |
| MAO-BTooltip Monoamine oxidase B | >100,000 (IC$_{50}$) (rat) |
| Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs: ||
The drug's affinity (K$_i$) for the serotonin 5-HT$_{2A}$ receptor has been found to be 1,300 nM. Its EC$_{50}$Tooltip half-maximal effective concentration at the receptor was 190 nM and its E$_{max}$Tooltip maximal efficacy was 84%. 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. TMA-2 is inactive at the monoamine transporters. 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.

## Legal status

As of 2011, TMA-2 is not an explicitly controlled substance in the United States. 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.