Peyote Alkaloids

More than 55 alkaloids have been isolated from peyote. Mescaline (3,4,5-trimethoxy-j8-phenethylamine) is the primary psychoactive alkaloid of the peyote cactus, and by far the one that has been most studied (figure 9.6). These may be categorized into phenethylamines (including mescaline), isoquinolones, and Krebs acid conjugates. See table 9.2 for a partial list of peyote alkaloids. 

Little is known specifically about the effects of mescaline compared to LSD. Much information about it relies upon its similarities with other monoamine hallucinogens. The majority of attention is given here to mescaline, but some brief mention of the diverse effects of other peyote alkaloids (of which little is known) is deserved. Often, their effects are very different from mescaline. Many alkaloids are present in sufficent concentrations to alter human physiology after oral consumption of peyote. Lophophorine in humans causes a "sickening feeling in the back of... 

GLC DATA FOR PEYOTE ALKALOIDS AND RELATED COMPOUNDS ON PACKED COLUMNS OF VARIOUS POLARITY2... 

The alkaloids salsolidine (48) and carnegine (49) show an obvious structural relationship to the peyote alkaloids (43) and (47) and evidence36 has been obtained for a related biosynthesis. Thus, in both systems alternative routes from tyrosine to dopamine are in operation involving tyramine and dopa respectively (Scheme 7).29,30,36 By analogy with peyote alkaloid biosynthesis, the C2 unit C(l) + C(9) would be expected to derive from pyruvic acid, and therefore the failure of this residue to incorporate activity from methionine is not unexpected. 

Bruhn, J.G. et al. 1978. Peyote alkaloids Identification in a prehistoric specimen of Lophophora from Coahuila, Mexico Science 199 1437-1438. 

Peyote Alkaloids.—An O-methyltransferase has been isolated from the peyote cactus. Its ability to catalyse the methylation of various phenolic phenethylamines and isoquinolines, and the site of methylation, has indicated possible biosynthetic relationships within the peyote cactus cf. ref. 3. 

An important series of in vivo experiments by Kapadia and his colleagues using [ C]-labeled precursors has led to a substantial advance in our understanding of the biogenesis of tetrahydroisoquinoline alkaloids. iV-Acetyl-3-demethylmescaline can act as a precursor for a variety of peyote alkaloids since administration of this amide, labeled as indicated, to peyote, Lophophora williamsii (Lemaire) Coult., generated radioactive anhalamine and anhalonidine. 

Ltjndstrom, j., and S. Agtjrell Thin-layer chromatography of peyote alkaloids. J. Chromatog, 30, 271 (1967). 

Kapadia G, Fayez MBE (1973) The chemistry of peyote alkaloids. Lloydia 36 9-35 Krane BD, Shamma M (1982) The isoquinolone alkaloids. J Nat Prod 45 377-384 Kunitomo J-I, Murakami Y, Oshikata M, Shingu T, Lu S-T, Chen I-S, Akasu M (1981) The alkaloids of Stephania sasakii Hayata (13). On the tertiary minor bases. Yakugaku Zasshi 101 431-436... 

S contemporary Mexican groups. Peyote contains more than 50 alkaloids, the most important of which is mescaline. 

Not surprisingly, peyote enjoyed a brief period of use as a cardiac tonic. Recently, one of its alkaloids, hordenine, has been credited with antiseptic action against a wide spectrum of microorganisms. 

Mescaline and related alkaloids are found in varying amounts in cacti of the genera Lophophora, Gymnacalycium, Stensonia, Mammillaria, Ariocarpus, Opuntia, Trichocereus, Pelecyphora, and probably others. Members of the Native American Church do quite well with the dried cactus, but extraction of mescaline is desirable since the pure compound seems to produce fewer unpleasant side effects (e.g., nausea). For an excellent review on the occurrence and chemistry of the mescaline type compounds, see JPS 59,1699(1970) (cf. JPS 60,655(1971)). Various species of these cacti occur in southwestern U.S. as well as Central and South America and have been used by the Aztecs and others for millennia. For a good review of peyote see Lloydia 36,1-58(1973). 

Figure 5. An example of protoalkaloids. Mescaline is the alkaloid derived from L-tyrosine and extracted from the Peyote cactns (Lophophora williamsii) belonging to the Cactns family (Cactaceae). MescaUne has strong psychoactive and haUncinogenic properties. Peyote cactns grows in the desert areas of northern Mexico and the sonthern parts of the USA. This plant was nsed in Pre-Colnmhian America in the shamanic practice of local tribes.

Mescaline is an alkaloid isolated from the peyote cactus, species Lophophora williamsii or Anhalonium lewinii, that grows in the southwestern United States and in Mexico. Mescaline is found in buttons that grow on top of the plant. Aztec and Native American Indians used the buttons in religious rites and for treatment of snakebite, flu, and arthritis. Some street names include bad seed, blue caps, cactus buttons, devils root, mesc, moon, peyote, shaman, and tops. 

Mescaline [54-04-6] (2-(3,4,5-trimethoxyphenyl)ethylamine) is the active ingredient in mescal buttons (peyotl or peyote), which are the dried tops of the Mexican dumpling cactus l ophopora wilhamsi. Mescaline produces visual hallucinations on ingestion. Its possible use as a psychotomimetic drug in the field of mental health has been studied (see Alkaloids Psychopharmacologicalagents). 

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. 

Our explorations with peyote went on, and we were more and more impressed with the importance of the effects of this substance when taken by people with a motivation toward better understanding of themselves and of life, and when given by one with similar motivation and an awareness of the hazards of improper use. Later we experimented with the use of mescaline, the psychedelic alkaloid present in the peyote cactus, and found the effects to be identical with those we had obtained through the use of peyote itself. 

Dopamine may alternatively be formed from tyrosine via hydroxylation of L-dopa which is decarboxylated. However, inverse isotope dilution experiments to study the formation of dopamine and dopa have shown that this is probably a minor pathway in peyote (176). It has been shown that L-tyrosine is incorporated into alkaloids in peyote three times more efficiently than into protein (344). 4-Hydroxy-3-methoxyphenethylamine can be methylated to 3,4-dimethoxy-phenethylamine (homoveratrylamine), which may be viewed as a dead-end product in Scheme 2 (10, 203). Phenylalanine is probably not a precursor of the... 

The scientific examination of peyote stimulated by Lewin s enthusiasm resulted in the isolation of the principal psychoactive component in 1897. Arthur Heffter, Lewin s colleague and rival, made this identification by systematically ingesting a number of alkaloid "fractions made from peyote as in the case of psilocybin later, animal testing had been inconclusive as to their various psychoactivities. Heffter named the isolate compound"mezcalin (which soon became "mescaline ) and reported that "mescaline hydrochloride, 0.15 g, produces a pattern of symptoms which differs in only a few respects from the one obtained with the drug (peyote). ... 

In their four-volume The Cactaceae, written at the turn of the century, Britten and Rose describe 1,235 species of cacti the number of clearly identified species has since gone well beyond 3,000. Peyote is unusual among cacti, displaying spines only as a seedling. It has been found to produce more than sixty separate alkaloids and is thus, as Richard Evans Schultes described the plant, "a veritable chemical factory. In Peyote—The Divine Cactus, Edward... 

Since the designation and acceptance of the L diffusa species, Swedish investigators have re-examined the plant material used in Germany by Lewin and his associates. They found that it was composed of both L williamsii and L diffusa species, which look somewhat similar. However, 90 percent of the alkaloids in L diffusa are in the form of a sedative called "pellodne, with only trace amounts of mescaline present, so it s understandable that the initial studies came to different, contradictory conclusions. (Anderson recounts the complexities wrought by this error on page 136 of his authoritative Peyote—The Divine Cactus.)... 

Trichoceri grow much faster than peyote—which may take five years when grown from seeds to reach a 3A-inch diameter—and they contain only a few alkaloids in addition to mescaline. When planted in shallow soil, halfinch slices from the cactus root easily. A two-foot-high San Pedro grows an additional four inches or so in about half a year. 

Most of the alkaloids found in peyote have never been tried on humans in pure form. Only four of these besides mescaline have been described subjectively. Much of this work was done by Arthur Heffter, who identified mescaline back in 1897. In 1977, Alexander Shulgin summarized the human tests at a conference in San Francisco ... 

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