# 2,5-Dimethoxyamphetamine

2,5-Dimethoxyamphetamine (2,5-DMA), also known as DMA-4 or as DOH, is a drug of the phenethylamine and amphetamine families. It is one of the dimethoxyamphetamine (DMA) series of positional isomers. The drug is notable in being the parent compound of the DOx (4-substituted-2,5-dimethoxyamphetamine) series of drugs.

## Use and effects

2,5-DMA is said to be inactive as a psychedelic, at least at the doses that have been assessed. However, it has been reported to produce some stimulant-like effects, as well as sympathomimetic effects and mydriasis. The dose range is said to be 80 to 160 mg orally and its duration is 6 to 8 hours.

## Pharmacology

2,5-DMA activities :
| Target | Affinity (K$_i$, nM) |
| 5-HT$_{1A}$ | 2,583 |
| 5-HT$_{1B}$ | 8,435 (rat) |
| 5-HT$_{1D}$ | ND |
| 5-HT$_{1E}$ | ND |
| 5-HT$_{1F}$ | ND |
| 5-HT$_{2A}$ | 211–5,200 (K$_i$) 160–3,548 (EC$_{50}$Tooltip half-maximal effective concentration) 58–109% (E$_{max}$Tooltip maximal efficacy) |
| 5-HT$_{2B}$ | 1,039 (K$_i$) >10,000 (EC$_{50}$) ND (E$_{max}$) |
| 5-HT$_{2C}$ | 104–>10,000 (K$_i$) 3,144 (EC$_{50}$) 76% (E$_{max}$) |
| 5-HT$_3$–5-HT$_7$ | ND |
| α$_{1A}$, α$_{1B}$–α$_{1D}$ | ND |
| α$_{2A}$–α$_{2C}$ | ND |
| β$_1$, β$_2$ | ND |
| D$_1$ | ND |
| D$_2$ | >7,000 |
| D$_3$–D$_5$ | ND |
| H$_1$–H$_4$ | ND |
| M$_1$–M$_5$ | ND |
| TAAR$_1$ | >10,000 (EC$_{50}$) (human) |
| I$_1$ | ND |
| σ$_1$, σ$_2$ | ND |
| SERTTooltip Serotonin transporter | >7,000 (K$_i$) ND (IC$_{50}$Tooltip half-maximal inhibitory concentration) ND (EC$_{50}$) |
| NETTooltip Norepinephrine transporter | >7,000 (K$_i$) ND (IC$_{50}$) ND (EC$_{50}$) |
| DATTooltip Dopamine transporter | >7,000 (K$_i$) ND (IC$_{50}$) ND (EC$_{50}$) |
| MAO-ATooltip Monoamine oxidase A | >100,000 (IC$_{50}$) |
| MAO-BTooltip Monoamine oxidase B | >100,000 (IC$_{50}$) |
| Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs: ||
2,5-DMA is a low-potency serotonin 5-HT$_{2A}$ receptor partial agonist, with an affinity (K$_i$) of 2,502 nM, an EC$_{50}$Tooltip half-maximal effective concentration of 160 to 3,548 nM (depending on the signaling cascade and study), and an E$_{max}$Tooltip maximal efficacy of 66 to 109%. It has also been assessed at several other receptors. The drug did not appear to bind to the monoamine transporters, at least at the assessed concentrations (up to 7,000 nM). It was inactive at the human trace amine-associated receptor 1 (TAAR1). 2,5-DMA shows dramatically reduced potency as a serotonin 5-HT$_{2A}$ receptor agonist compared to the DOx drugs, such as 2,5-dimethoxy-4-methylamphetamine (DOM).
Though 2,5-DMA appears to be inactive or of very low potency as a psychedelic in humans, it is a highly potent anti-inflammatory drug similarly to other DOx and 2C drugs. This was in spite of it being of very low potency as a serotonin 5-HT$_{2A}$ receptor agonist in terms of calcium mobilization in the study (EC$_{50}$ = 3,548 nM; E$_{max}$ = 109.0%). Based on the preceding findings, Charles D. Nichols has said that both fully anti-inflammatory non-psychedelic compounds like 2,5-DMA and fully psychedelic non-anti-inflammatory compounds like DOTFM are known.