Mescaline 3,4,5-trimethoxyphenethylamine

Mescaline (3,4,5-trimethoxyphenethylamine) (Fig. 5) is mainly contained in Lophophora williamsii peyote, a cactus native to the deserts of Mexico. Peyote contains an average of about 1.5 % of mescaline. It is often synthetic and looks like a clear powder with colors ranging from white to brown, depending on purity. 

EXTENSIONS AND COMMENTARY There was absolutely no reason to suspect that the simple rearrangement of the methoxy groups of TMA from the classic 3,4,5-positions to this new, 2,4,5-orientation, would dramatically increase potency like this. Mescaline, 3,4,5-trimethoxyphenethylamine, is an extraordinary compound, but it is not particularly potent. 

Little work has been done in this area. Clark et al. (36), however, reported that mescaline is more extensively deaminated by a soluble rabbit liver amine oxidase preparation than is 2,4,5-trimethoxyphenethylamine. One should also note that the addition of the alpha-methyl will increase the octanol-water partition... 

The phenethylamine homologue of TMA-6 is well known, but is virtually unexplored pharmacologically. The above benzaldehyde with nitromethane in glacial acetic acid containing ammonium acetate gave the appropriate beta-nitrostyrene as yellow crystals with a mp 177-177.5 °C. This, with LAH in ether, gave 2,4,6-trimethoxyphenethylamine (2,4,6-TMPEA, or 2C-TMA-6) as the picrate salt (mp 204-205 °C) or the hydrochloride salt (mp 234-235 °C). It has been shown not to be a substrate to the soluble amine oxidase from rabbit liver, a property it shares with mescaline, but whether it is or is not active in man is at present unknown. 

One part is the large collection of psychoactive compounds known as the phenethylamines. The first known plant psychedelic was mescaline, or 3,4,5-trimethoxyphenethylamine. This simple one-ring alkaloid was discovered in the North American dumpling cactus Peyote (Anhalonium williamsii) in the late nineteenth century, and is now known to be a component of over fifty other cacti. Over a dozen other cactus phenethylamines have been isolated and identified, and there are perhaps a hundred synthetic analogues that are now also known to be psychedelic in action. This body of information has been published by my wife Ann and me as a book entitled "PIHKAL A Chemical Love Story." PIHKAL stands for Phenethylamines I Have Known and Loved. 

EXTENSIONS AND COMMENTARY The 4 and the beta-D are two of five obvious deuterium isomer derivatives of mescaline. The three remaining are (1) 3,5-D (4-methoxy-3,5-bis-trideuteromethoxyphenethylamine) (2) 2,6-D (2,6-di-deutero-3,4,5-trimethoxyphenethylamine) and (3) alpha-D (alpha,alpha-dideutero-3,4,5-tri-methoxyphenethylamine). I fully expect both 3,5-D and 2,6-D to be indistinguishable from mescaline in effect, since it is known that not much metabolism takes place in man at these locations of the molecule. 

QUALITATIVE COMMENTS (with less than 300 mg) Since it was not easy, however, to judge the extent of a Rausch -action from experiments on animals, some injections of beta-2,4,5-trimethoxyphenethylamine were administered to the author, and finally a control test was carried out with an equal quantity of mescaline. The action of both these substances in these experiments agreed only to a limited extent with the effects described for mescaline by, for example, Beringer. It... 

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