3,4,5-Trimethoxyamphetamine

3,4,5-Trimethoxyamphetamine, also known as α-methylmescaline or mescalamphetamine, is a psychedelic drug of the phenethylamine and amphetamine families. It is one of the trimethoxyamphetamine series of positional isomers. The drug is notable in being the amphetamine analogue of mescaline.

Use and effects

In his book PiHKAL, Alexander Shulgin lists TMA's dose as 100 to 250mg orally and its duration as 6 to 8hours. For comparison, mescaline is typically used at doses of 200 to 500mg orally and is said to have a duration of 10 to 12hours or longer. TMA's positional isomer 2,4,5-trimethoxyamphetamine is much more potent than TMA, with a dose of 20 to 40mg orally and a duration of 8 to 12hours.
The effects of TMA have been reported to include closed-eye imagery, introspection, music enhancement, emotional volatility, annoyance and irritability, feeling violent, lightheadedness, giddiness, and nausea, among others. It is said to lack mescaline's color changes and to have a "thread of negativity" at higher doses and a possible "antisocial nature" that has limited interest in the drug.

TMA is a low-potency serotonin 5-HT_2A receptor partial agonist, with an affinity of >12,000nM, an of 1,700nM, and an of 40%. Conversely, it was inactive at the serotonin 5-HT_1A, 5-HT_2B and 5-HT_2C receptors and at several other receptors, at least at the assessed concentrations. It showed affinity for the mouse and rat trace amine-associated receptor 1, whereas it was inactive at the human TAAR1.
TMA is also a very low-potency serotonin releasing agent, with an value of 16,000nM. In contrast, it is inactive as a releasing agent and reuptake inhibitor of dopamine and norepinephrine. Despite its apparent SRA activity in vitro, TMA did not increase brain serotonin or dopamine levels in rodents in vivo. TMA is similarly inactive as a monoamine oxidase inhibitor, including of both monoamine oxidase A and monoamine oxidase B .
The low potency of TMA as a serotonin 5-HT_2A receptor agonist is analogous to the case of mescaline, which is a well-known and widely used psychedelic but is likewise a very low-potency agonist of this receptor, showing an affinity of 9,400nM, an of 10,000nM, and an of 56% in the same study. For comparison, DOM has shown an affinity of 88nM and an of 4 to 24nM.

The chemical synthesis of TMA has been described.

A variety of derivatives of TMA, known as the 3C series, have been studied and described.

TMA was first synthesized by Gordon Alles around 1937. He assessed it in both animal studies and self-experiments and documented its effects, but these were not reported until 1959. The drug was first described in the scientific literature in 1947 and its psychedelic effects were first described in 1955. TMA was studied at Edgewood Arsenal under the code name EA‐1319 in 1953 and 1954. The drug was further characterized by Alexander Shulgin and described in his 1991 book PiHKAL.