2,4,5-Trimethoxyamphetamine
Pharmaceutical compound
From Wikipedia, the free encyclopedia
2,4,5-Trimethoxyamphetamine (2,4,5-TMA), also known as TMA-2, MMM, or 2,5-dimethoxy-4-methoxyamphetamine (DOMeO), is a psychedelic drug of the phenethylamine and amphetamine families.[1][2][3] It is one of the trimethoxyamphetamine (TMA) series of positional isomers.[1][2] The drug is also notable in being the 4-methoxylated member of the DOx (i.e., 4-substituted-2,5-dimethoxyamphetamine) series of drugs.[1][2]
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| Other names | TMA-2; 2,4,5-TMA; 2,4,5-Trimethoxy-α-methylphenethylamine; 2,5-Dimethoxy-4-methoxyamphetamine; 4-Methoxy-2,5-dimethoxyamphetamine; DOMeO; DOOMe; DOO; MMM; β-Aminodihydroasarone |
| Routes of administration | Oral[1][2][3] |
| Drug class | Serotonergic psychedelic; Hallucinogen |
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| Onset of action | ≥1 hour[3] |
| Duration of action | 8–12 hours[1][2][3] |
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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-2's dose as 20 to 40 mg orally and its duration as 8 to 12 hours.[1][2][3][5] In earlier publications, it was described that threshold effects occur at a dose of 10 mg orally, an effective dose is 16 to 20 mg orally, its onset of psychoactive effects is after 1 hour, and a plateau of effects occurs from 3 to 6 hours following administration.[3][6] The drug is much more potent than its positional isomer 3,4,5-trimethoxyamphetamine (3,4,5-TMA, TMA, or TMA-1), which is said to be active at doses of 100 to 250 mg orally and to have a duration of 6 to 8 hours.[7] However, DOM (2,5-dimethoxy-4-methylamphetamine), the analogue of TMA-2 in which its 4-methoxy group has been replaced with a more lipophilic 4-methyl group, is about 10 times more potent than TMA-2.[8] TMA-2 has been said to have a sharp dose–response curve, with several additional toxic symptoms occurring at doses of 25 to 30 mg.[3]
The effects of TMA-2 have been reported to include color and contrast enhancement, closed-eye imagery like kaleidoscopic images, visuals such as visual distortion and movement, auditory enhancement, increased salience of objects in one's environment, cosmic thinking, time dilation, and music and erotic enhancement.[1][2][3] Other effects have been reported to include confusion, lethargy, laziness, sleepiness, lightheadedness, feeling faintish and actual fainting, brief but repeated periods of amnesia, fear of psychosis, pupil dilation, paresthesia, nausea, vomiting, abdominal cramps, diarrhea, and muscle tremors, among others.[1][2][3] The drug was described as a "seminal" or "archetypal" psychedelic in PiHKAL.[1]
Interactions
Combination of TMA-2 with harmaline or ibogaine has been reported to result in long-lasting episodes complicated by severe psychomotor agitation.[3][6]
Pharmacology
Pharmacodynamics
| Target | Affinity (Ki, nM) |
|---|---|
| 5-HT1A | >10,000 |
| 5-HT1B | >10,000 |
| 5-HT1D | >10,000 |
| 5-HT1E | >10,000 |
| 5-HT1F | ND |
| 5-HT2A | 57.9–1,300 (Ki) 190–1,860 (EC50) 84–102% (Emax) |
| 5-HT2B | 154–307 (Ki) 270 (EC50) 78% (Emax) |
| 5-HT2C | 87.7–5,300 |
| 5-HT3 | >10,000 |
| 5-HT4 | ND |
| 5-HT5A | >10,000 |
| 5-HT6 | >10,000 |
| 5-HT7 | >10,000 |
| α1A, α1B | >10,000 |
| α1D | ND |
| α2A–α2C | >10,000 |
| β1, β2 | >10,000 |
| D1–D5 | >10,000 |
| H1 | 1,407 |
| H2–H4 | >10,000 |
| M1, M3, M4 | ND |
| M2, M5 | >10,000 |
| TAAR1 | >4,400 (Ki) (mouse) 3,100 (Ki) (rat) ND (EC50) (human) |
| I1 | ND |
| σ1, σ2 | ND |
| SERT | >10,000 (Ki) >100,000 (IC50) >100,000 (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 | >100,000 (IC50) (rat) |
| MAO-B | >100,000 (IC50) (rat) |
| Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs: [9][10][11][12][13][14][15][16][17] | |
TMA-2's affinity (Ki) for the serotonin 5-HT2A receptor has been found to be 1,300 nM.[12] Its EC50 at the receptor was 190 nM and its Emax was 84%.[12] The drug was also active at the serotonin 5-HT2B receptor and, to a much lesser extent, at the serotonin 5-HT2C receptor.[12] In an earlier study, its affinities (Ki) were 1,650 nM at the serotonin 5-HT2 receptor and 46,400 nM at the serotonin 5-HT1 receptor.[18][19] TMA-2 is inactive at the monoamine transporters.[16][12] It was inactive at the mouse trace amine-associated receptor 1 (TAAR1), whereas it bound to the rat TAAR1 with an affinity (Ki) of 3,100 nM and was not assessed at the human TAAR1.[12]
Pharmacokinetics
In terms of metabolism, TMA-2 is known to be at least partially O-demethylated in animals in vivo.[3][6] It might produce 2,4,5-trihydroxyamphetamine (THA) as a metabolite.[3] The pharmacokinetics and metabolism of TMA-2 in humans are unknown.[3][6]
Chemistry
Properties
The chemical properties of TMA-2 have been described.[3]
Synthesis
The chemical synthesis of TMA-2 has been described.[1]
Analogues and derivatives
TMA-2 (2,4,5-trimethoxyamphetamine) is very similar in chemical structure to the monoaminergic neurotoxin 6-hydroxydopamine (2,4,5-trihydroxyphenethylamine).[3][6]
A variety of derivatives of TMA-2 (MMM) have been developed and studied, such as MEM among others.[12][20]
History
TMA-2 was first described in the scientific literature by Viktor Bruckner in 1933.[21][2][3][22] Subsequently, Alexander Shulgin discovered the hallucinogenic effects of TMA-2 in 1962 and published them in 1964.[3][21][23][24][2] The drug was later described in further detail by Shulgin in his 1991 book PiHKAL (Phenethylamines I Have Known and Loved).[1]
Society and culture
Legal status
Canada
TMA-2 is a controlled substance in Canada.[25]
United States
TMA-2 is not an explicitly controlled substance in the United States.[2][4] However, it is a positional isomer of 3,4,5-trimethoxyamphetamine (TMA), and thus may be considered a Schedule I controlled substance in this country similarly to TMA.[2][3][4][26]
See also
- Trimethoxyamphetamine
- Substituted methoxyphenethylamine
- 2,4,5-Trimethoxyphenethylamine (2,4,5-TMPEA; 2C-O)
- 2,5-Dimethoxyamphetamine (2,5-DMA; DMA-4; DOH)
- 2,4-Dimethoxyamphetamine (2,4-DMA; DMA-3)