 | |
| Clinical data | |
|---|---|
| Other names | TMT; MCPA;trans-2-(3,4,5-Trimethoxyphenyl)cyclopropylamine |
| Drug class | Possibleserotonergic psychedelic orhallucinogen |
| ATC code |
|
| Identifiers | |
| |
| CAS Number | |
| PubChemCID | |
| ChemSpider | |
| CompTox Dashboard(EPA) | |
| Chemical and physical data | |
| Formula | C12H17NO3 |
| Molar mass | 223.272 g·mol−1 |
| 3D model (JSmol) | |
| |
| |
3,4,5-Trimethoxytranylcypromine (TMT), also known asMCPA as well astrans-2-(3,4,5-trimethoxyphenyl)cyclopropylamine, is a possiblepsychedelic drug of thephenethylamine,scaline, andphenylcyclopropylamine families related tomescaline (3,4,5-trimethoxyphenethylamine).[1][2][3][4] It is acyclized phenethylamine and theanalogue of mescaline in which the α and β positions of theethylside chain have beencyclized to form acyclopropanering.[2][3][4] The drug may also be thought of as astructural hybrid between mescaline and theantidepressanttranylcypromine.[2][5][6]
In his bookPiHKAL (Phenethylamines I Have Known and Loved),Alexander Shulgin reported that TMT produced nocentral effects at a dose of 13 mgorally.[2] Higher doses were not assessed.[2]
TMT has been reported to producemescaline-like effects in animals with similar or slightly greaterpotency than mescaline but a slightly shorterduration.[7][5][6][8][3][4] TMT is thetrans isomer of a pair ofcis andtransisomers, and it is specifically thetrans isomer that is active.[7][6][8][9][10][11][3][4]
TMT was first described in thescientific literature by G. C. Walters and P. D. Cooper in 1968.[5]Alexander Shulgin subsequently described evaluating a low dose of TMT in humans in his 1991 bookPiHKAL (Phenethylamines I Have Known and Loved).[2] TMT was one of the earliest psychedelic-relatedcyclized phenethylamines to be evaluated.[7][3][4] Subsequently, the much morepotent2,5-dimethoxy-4-methylphenylcyclopropylamine (DMCPA) was developed.[3][4]
TMT is not acontrolled substance inCanada as of 2025.[12]
Incorporation of the α-methyl into a cyclopropane ring gives substituted 2-phenylcyclopropylamines with high potency, both in vitro and in vivo. In vivo potency for the cis- and trans-cyclopropane analogs of mescaline was first reported by Cooper and Walters.94,95 These workers found that the trans compound 59 produced effects in rodents that qualitatively resembled mescaline, with a potency somewhat greater than mescaline and a slightly shorter duration of action (Figure 26). Aldous et al.50 subsequently explored several cyclopropane analogs of substituted amphetamines. Although it was not then possible to measure receptor effects, production of hyperthermia in rabbits as well as producing changes in cat encephaolgram (EEG) were taken as indicators of possible hallucinogenic action, which we now know is correlated with actions at the 5-HT2A receptor. In particular, the trans-2,4,5- trimethoxy 60 and trans-2,5-dimethoxy-4-methyl compounds 61 had hallucinogen-like activity, with about 20 and 35%, respectively, of the activity of DOM.
Incorporating the alpha methyl into a cyclopropane ring gives substituted 2-phenylcyclopropylamines with high in vitro and in vivo potency. The cis and trans cyclopropane analogues of mescaline were first reported by Cooper and Walters, who found that trans compound 64 produced an effect in rodents qualitatively resembling mescaline, but with a potency slightly greater than mescaline (Walters and Cooper 1968; Cooper and Walters 1972). Subsequently Aldous et al. (1974) explored cyclopropane analogues of several substituted amphetamines. Using an assay that measured hyperthermia in rabbits, as well as assessing changes in cat EEG, trans-2,4,5-trimethoxy compound 65 and trans-2,5-dimethoxy-4-methyl compound 66 (DMCPA) had hallucinogen-like activity, with about 20 and 35%, respectively, of the activity of DOM (37).
Table 3.8.—RELATIVE HALLUCINOGENIC POTENCIES OF SOME 2-PHENYLCYCLOPROPYLAMINES [...]
[Cooper and Walters (1972)] demonstrated mescaline-like activity in animals for trans-2-(3,4,5-trimethoxyphenyl)-cyclopropylamine 1. In contrast, the cis isomer would have been expected to be more active on the basis of the indole mimicry hypothesis. More recently, Aldous et al. (1974) examined a series of 2-phenylcyclopropylamines as potential hallucinogens. Notable in this study were the results obtained for trans-2-(2,5-dimethoxy-4-methylphenyl)-cyclopropylamine 2, an analogue of DOM. This compound was reported to have about one-third the potency of DOM. These studies led to the clear conclusion that the side chain of the phenethylamine hallucinogens must assume a transoid conformation.
Rigid Analogs—Several rigid analogs of phenethylamine hallucinogens have been evaluated to elucidate the binding conformation of the side chain. To date, none has been particularly revealing, although some interesting findings have emerged. The simplest rigid analogs are the substituted 2-phenylcyclopropylamines. The 3,4,5-trimethoxy compounds (XXX and XXXI) first were prepared as mescaline analogs (101). Inactivity for the cis-isomer (XXXI) seems to establish conclusively the side-chain binding conformation as trans in the flexible phenethylamines.
However, the α-methyl group of the amphetamine can be incorporated into a cyclopropane ring with retention of activity. Cooper and Walters (1972) first compared the cis and trans cyclopropylamine analogs of mescaline for behavioral activity in rat. Only the trans compound (45) was active. Aldous et al. (1974) subsequently examined several trans cyclopropylamine analogs of hallucinogenic amphetamines. This group reported that these congeners had activity and potency similar to those of their amphetamine counterparts. The cyclopropylamine analog of DOM, DMCPA (46), first reported by this group subsequently was resolved into its enantiomers, which were tested by Nichols et al. (1979). The 1R,2S-(−) enantiomer (46, as shown) proved to be most active. This result is, perhaps, not surprising since the stereochemistry at the a carbon of the cyclopropyl ring is identical to that of the R isomer of the amphetamines. Further, although the difference in affinity for the 5-HT2 receptor between the Rand S enantiomers of the amphetamines was small, Johnson et al. (1990b) reported that the enantiomer of DMCPA have a ~30-fold difference in affinity.
