3,4,5-Trimethoxyamphetamine
Pharmaceutical compound
From Wikipedia, the free encyclopedia
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.[1][2] It is one of the trimethoxyamphetamine (TMA) series of positional isomers.[1][2] The drug is notable in being the amphetamine (α-methylated) analogue of mescaline (3,4,5-trimethoxyphenethylamine).[1][2]
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| Other names | Trimethoxyamphetamine; TMA; TMA-1; 3,4,5-TMA; α-Methylmescaline; alpha-Methylmescaline; AMM; Mescalamphetamine; 3,4,5-Trimethoxy-α-methylphenethylamine; EA‐1319; EA1319; 3C-Mescaline; 3C-M |
| Routes of administration | Oral[1][2] |
| Drug class | Serotonergic psychedelic; Hallucinogen; Serotonin 5-HT2A receptor agonist |
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| Duration of action | 6–8 hours[1][2] |
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| Formula | C12H19NO3 |
| Molar mass | 225.288 g·mol−1 |
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Use and effects
In his book PiHKAL (Phenethylamines I Have Known and Loved), Alexander Shulgin lists TMA's dose as 100 to 250 mg orally and its duration as 6 to 8 hours.[1][2][4][5] For comparison, mescaline is typically used at doses of 200 to 500 mg orally and is said to have a duration of 10 to 12 hours or longer.[6] 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 40 mg orally and a duration of 8 to 12 hours.[7]
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.[1] 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.[1]
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 | ND |
| 5-HT2A | >10,000 (Ki) 41.3–1,700 (EC50) 40–96% (Emax) |
| 5-HT2B | 477 (Ki) >10,000 (EC50) |
| 5-HT2C | 4,600–>10,000 (Ki) 47.4 (EC50) 92% (Emax) |
| 5-HT3 | >10,000 |
| 5-HT4 | ND |
| 5-HT5A | >10,000 |
| 5-HT6 | >10,000 |
| 5-HT7 | 749 |
| α1A, α1B | >10,000 |
| α1D | ND |
| 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 | ND |
| M2, M5 | >10,000 |
| nACh | 260–>10,000 |
| TAAR1 | 1,800 (Ki) (mouse) 3,200 (Ki) (rat) >10,000 (EC50) (human) |
| I1 | >10,000 |
| σ1 | 537 |
| σ2 | 537 |
| SERT | >10,000 (Ki) >100,000 (IC50) 16,000 (EC50) (rat) |
| NET | >10,000 (Ki) >100,000 (IC50) >100,000 (EC50) (rat) |
| DAT | >10,000 (Ki) >100,000 (IC50) >100,000 (EC50) (rat) |
| MAO-A | >200,000 (IC50) |
| MAO-B | >200,000 (IC50) |
| Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs: [8][9][10][11][12][13][14][15] | |
TMA is a low-potency serotonin 5-HT2A receptor partial agonist, with an affinity (Ki) of >12,000 nM, an EC50 of 1,700 nM, and an Emax of 40%.[11] 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 10,000 nM).[11] It showed affinity for the mouse and rat trace amine-associated receptor 1 (TAAR1) (Ki = 1,800 nM and 3,200 nM, respectively), whereas it was inactive at the human TAAR1 (EC50 > 10,000 nM).[11]
TMA is also a very low-potency serotonin releasing agent (SRA), with an EC50 value of 16,000 nM.[12] In contrast, it is inactive as a releasing agent and reuptake inhibitor of dopamine and norepinephrine (EC50 > 100,000 nM).[12] Despite its apparent SRA activity in vitro, TMA did not increase brain serotonin or dopamine levels in rodents in vivo.[15] TMA is similarly inactive as a monoamine oxidase inhibitor (MAOI), including of both monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B) (IC50 > 200,000 nM).[14][15]
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 9,400 nM, an EC50 of 10,000 nM, and an Emax of 56% in the same study.[11] For comparison, DOM has shown an affinity (Ki) of 88 nM and an EC50 of 4 to 24 nM.[16]
Chemistry
Synthesis
The chemical synthesis of TMA has been described.[1]
Derivatives
A variety of derivatives of TMA, known as the 3C series, have been studied and described.[1][2][11]
History
TMA was first synthesized by Gordon Alles around 1937.[17][18] He assessed it in both animal studies and self-experiments and documented its effects, but these were not reported until 1959.[17][18] The drug was first described in the scientific literature in 1947 and its psychedelic effects were first described in 1955.[19][20][21][22] TMA was studied at Edgewood Arsenal under the code name EA‐1319 in 1953 and 1954.[17] The drug was further characterized by Alexander Shulgin and described in his 1991 book PiHKAL (Phenethylamines I Have Known and Loved).[1][2]
Society and culture
Legal status
Canada
TMA is a controlled substance in Canada.[23]
United States
TMA is a Schedule I controlled substance in the United States.[2][3]
See also
- Trimethoxyamphetamine
- Substituted methoxyphenethylamine
- 3C (psychedelics) (4-substituted 3,5-dimethoxyamphetamines)
- Mescaline (3,4,5-trimethoxyphenethylamine; 3,4,5-TMPEA; TMPEA)
- α-Ethylmescaline (3,4,5-trimethoxy-α-ethylphenethylamine)
- Methyl-TMA (N-methyl-TMA)
- 3,4-Dimethoxyamphetamine (3,4-DMA)