3,5-Dimethoxyamphetamine

3,5-Dimethoxyamphetamine (3,5-DMA), also known as DMA-6, is a drug of the amphetamine family and a positional isomer of dimethoxyamphetamine (DMA). It is the parent structure of the 3C (4-substituted 3,5-dimethoxyamphetamine) family of compounds (also known as 3C-scalines).

In an early study, it showed similar affinity for serotonin receptors as mescaline (3,4,5-trimethoxyphenethylamine) but had more than an order of magnitude lower affinity than DOx (4-substituted 2,5-dimethoxyamphetamine) drugs like DOM, DOET, and DOB. However, in a later study, it showed no or very low affinity for the serotonin 5-HT_2A and 5-HT_2C receptors (K_i = >10,000 nM), whereas DOB showed high affinity for these receptors (K_i = 32 nM and 64 nM, respectively). 3,5-DMA's effects on monoamine reuptake and efflux have also been studied. It appeared to be weak or inactive as a norepinephrine reuptake inhibitor and norepinephrine releasing agent. Likewise, it was a very weak serotonin reuptake inhibitor (IC₅₀Tooltip half-maximal inhibitory concentration = 18,500 nM) and serotonin releasing agent (active at ≥10,000 nM).

3,5-DMA was inactive in substituting for DOM in rodent drug discrimination tests (4–14% appropriate responding for 5–12.5 mg/kg), suggesting that it would not be hallucinogenic in humans. However, it has shown other pharmacological effects in mice and with similar potency as mescaline, whereas it was inactive in rats. The effects of 3,5-DMA in humans have not been reported. 3,5-DMA has been detected as an adulterant in forensic drug samples. As a positional isomer of 2,5-dimethoxyamphetamine (2,5-DMA; DMA-4), 3,5-DMA is a Schedule I controlled substance in the United States.

A derivative of 3,5-DMA, 4-bromo-3,5-dimethoxyamphetamine (4-Br-3,5-DMA), showed relatively high affinity for the serotonin 5-HT_2A and 5-HT_2C receptors (K_i = 210 nM and 570 nM, respectively). However, it was not active as a psychedelic at the assessed doses (4–10 mg).