3,4,5-Trimethoxyamphetamine (TMA, TMA-1, or 3,4,5-TMA), also known as α-methylmescaline (3C-mescaline or 3C-M) or mescalamphetamine, is a psychedelic drug of the phenethylamine and amphetamine families. It is one of the trimethoxyamphetamine (TMA) series of positional isomers. The drug is notable in being the amphetamine (α-methylated) analogue of mescaline (3,4,5-trimethoxyphenethylamine).

Use and effects In his book PiHKAL (Phenethylamines I Have Known and Loved), 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 (2,4,5-TMA or TMA-2) 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.

Interactions

Pharmacology Pharmacodynamics + Target Affinity (Ki, nM) 5-HT1A 1,678–>5,600 5-HT1B 2,855 5-HT1D 3,035 5-HT1E 3,369 5-HT1F 5-HT2A >10,000 (Ki)41.3–1,700 ()40–96% () 5-HT2B 477 (Ki)>10,000 () 5-HT2C 4,600–>10,000 (Ki)47.4 ()92% () 5-HT3 >10,000 5-HT4 5-HT5A >10,000 5-HT6 >10,000 5-HT7 749 α1A, α1B >10,000 α1D α2A 2,071–4,030 α2B >10,000 α2C 5,014 β1, β2 >10,000 D1–D5 >10,000 H1–H4 >10,000 M1, M3, M4 M2, M5 >10,000 nACh 260–>10,000 TAAR1 1,800 (Ki) (mouse)3,200 (Ki) (rat)>10,000 () (human) I1 >10,000 σ1 537 σ2 537 >10,000 (Ki)>100,000 ()16,000 () (rat) >10,000 (Ki)>100,000 ()>100,000 () (rat) >10,000 (Ki)>100,000 ()>100,000 () (rat) >200,000 () >200,000 () Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs:

TMA is a low-potency serotonin 5-HT2A receptor partial agonist, with an affinity (Ki) of >12,000nM, an of 1,700nM, and an of 40%. Conversely, it was inactive at the serotonin 5-HT1A, 5-HT2B and 5-HT2C receptors and at several other receptors, at least at the assessed concentrations (up to 10,000nM). It showed affinity for the mouse and rat trace amine-associated receptor 1 (TAAR1) (Ki = 1,800nM and 3,200nM, respectively), whereas it was inactive at the human TAAR1 ( > 10,000nM).

TMA is also a very low-potency serotonin releasing agent (SRA), with an value of 16,000nM. In contrast, it is inactive as a releasing agent and reuptake inhibitor of dopamine and norepinephrine ( > 100,000nM). 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 (MAOI), including of both monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B) ( > 200,000nM).

The low potency of TMA as a serotonin 5-HT2A 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 (Ki) of 9,400nM, an of 10,000nM, and an of 56% in the same study. For comparison, DOM has shown an affinity (Ki) of 88nM and an of 4 to 24nM.

Chemistry Synthesis The chemical synthesis of TMA has been described.

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

History 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 (Phenethylamines I Have Known and Loved).

Society and culture Legal status Canada TMA is a controlled substance in Canada.

United States TMA is a Schedule I controlled substance in the United States.

See also Substituted methoxyphenethylamine α-Ethylmescaline (3,4,5-trimethoxy-α-ethylphenethylamine) Methyl-TMA (N-methyl-TMA) 3,4-Dimethoxyamphetamine (3,4-DMA)

References

External links TMA - Isomer Design TMA - PiHKAL - Erowid TMA - PiHKAL - Isomer Design