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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;Serotonin5-HT2A receptoragonist |
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| Pharmacokinetic data | |
| Duration of action | 6–8 hours[1][2] |
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| Chemical and physical data | |
| Formula | C12H19NO3 |
| Molar mass | 225.288 g·mol−1 |
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3,4,5-Trimethoxyamphetamine (TMA,TMA-1, or3,4,5-TMA), also known asα-methylmescaline (3C-mescaline or3C-M) ormescalamphetamine, is apsychedelic drug of thephenethylamine andamphetamine families.[1][2] It is one of thetrimethoxyamphetamine (TMA) series ofpositional isomers.[1][2] The drug is notable in being the amphetamine (i.e., α-methylated)analogue ofmescaline (3,4,5-trimethoxyphenethylamine).[1][2]
In his bookPiHKAL (Phenethylamines I Have Known and Loved),Alexander Shulgin lists TMA's dose as 100 to 250 mgorally and itsduration 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 isomer2,4,5-trimethoxyamphetamine (2,4,5-TMA or TMA-2) is much morepotent 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 includeclosed-eyeimagery,introspection,music enhancement,emotional volatility,annoyance andirritability, feelingviolent,lightheadedness,giddiness, andnausea, 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]
| 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 (EC50Tooltip half-maximal effective concentration) 40–96% (EmaxTooltip maximal efficacy) |
| 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 |
| SERTTooltip Serotonin transporter | >10,000 (Ki) >100,000 (IC50Tooltip half-maximal inhibitory concentration) 16,000 (EC50) (rat) |
| NETTooltip Norepinephrine transporter | >10,000 (Ki) >100,000 (IC50) >100,000 (EC50) (rat) |
| DATTooltip Dopamine transporter | >10,000 (Ki) >100,000 (IC50) >100,000 (EC50) (rat) |
| MAO-ATooltip Monoamine oxidase A | >200,000 (IC50) |
| MAO-BTooltip Monoamine oxidase 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-potencyserotonin5-HT2A receptorpartial agonist, with anaffinity (Ki) of >12,000 nM, anEC50Tooltip half-maximal effective concentration of 1,700 nM, and anEmaxTooltip maximal efficacy of 40%.[11] Conversely, it was inactive at the serotonin5-HT1A,5-HT2B and5-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 rattrace 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-potencyserotonin releasing agent (SRA), with anEC50 value of 16,000 nM.[12] In contrast, it is inactive as areleasing agent andreuptake inhibitor ofdopamine andnorepinephrine (EC50 > 100,000 nM).[12] Despite its apparent SRA activityin vitro, TMA did not increase brain serotonin or dopamine levels in rodentsin vivo.[15] TMA is similarly inactive as amonoamine oxidase inhibitor (MAOI), including of bothmonoamine oxidase A (MAO-A) andmonoamine oxidase B (MAO-B) (IC50Tooltip half-maximal inhibitory concentration > 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, anEC50 of 10,000 nM, and anEmax of 56% in the same study.[11] For comparison,DOM has shown an affinity (Ki) of 88 nM and anEC50 of 4 to 24 nM.[16]
Thechemical synthesis of TMA has been described.[1]
A variety ofderivatives of TMA, known as the3C series, have been studied and described.[1][2][11]
TMA was firstsynthesized byGordon Alles around 1937.[17][18] He assessed it in bothanimal studies andself-experiments and documented its effects, but these were not reported until 1959.[17][18] The drug was first described in thescientific literature in 1947 and its psychedelic effects were first described in 1955.[19][20][21][22] TMA was studied atEdgewood Arsenal under the code name EA‐1319 in 1953 and 1954.[17] The drug was further characterized byAlexander Shulgin and described in his 1991 bookPiHKAL (Phenethylamines I Have Known and Loved).[1][2]
TMA is aSchedule Icontrolled substance in theUnited States.[2][3]
For example, 3,4,5-trimethoxyamphetamine (TMA) is active at a dose range of 100–250 mg, whereas its 2,4,5-regioisomer (2,4,5-trimethoxyamphetamine, TMA-2) is active at 20–40 mg (Shulgin and Shulgin 1991).
Table 4 Human potency data for selected hallucinogens. [...]
