Phenethylamine alkaloids Mescaline

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. 

Of the alkaloids so far identified in just L. william-sii alone, 15 are Beta-phenethylamine and simple isoquinoline alkaloids. Mescaline, N-methylmescaline, N-acetylemescaline, anhalamine, anhalonine, anhalidine, anhalinine, anhalonidine, lophophorine, O-methylan-halondedine, and pellotine have all been identified as the principal components of the plant. However, only mescaline has so far been determined to cause hallucinations. 

The simple alkaloid mescaline is the main active component of L. ml-liamsii of (10) and o Trichocereus pachanoi of (12), and the yield of mescaline is said to be 2% of the dried material. Mescaline is a phenethylamine (=phenylethylamine) type alkaloid, like ephedrine. 

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. 

Key to alkaloids Dop, dopamine Epi, epinephrine Eph, ephedrine i/iEph, pseudoephedrine Homova, homoveratrylamine Hord, hordenine Macr, macromerine Mesc, mescaline Oct, octopa-mine Phe, phenethylamine Synephr, synephrine Tyr, tyramine. 

An improved method of preparation of cotarnine and opianic acid by the electrochemical oxidation of narcotine at a graphite anode in the presence of potassium dichromate has been described in a patent.3 In a study of the pharmacological effects of mescaline, the binding of the alkaloid with rat brain tissue has been examined, using 14C-labelled material.4 A technique for the separation, identification, and estimation of tyramine, methoxytyramine, and related phenethylamines by g.l.c. of their trimethylsilyl derivatives has been described in detail.5... 

Doetsch, EW. etal. 1980. Cactus alkaloids. XL. Identification of mescaline and other (3-phenethylamines inPereskia, Pereskiop-i/r, and Islaya by use of fiuorescamine con-JourmdofOrrormOographyr -. 79. 

Quite simply, mescaline is a major component and a centrally active alkaloid of the Peyote plant. It is a phenethylamine, which can undergo a cyclization within the plant to produce a pile of derivatives (tetrahydroisoquinolines) such as anhalonine and 0-methylanhalonidine that are marvelously complex alkaloids, all natural components of this magical cactus. But there is another pile of derivatives (tetrahydroisoquinolines) such as anhalonine, and lophophorine, and peyophorine which are the logical cyclization products of another phenethylamine which does not exist in the cactus. 

The Mexican peyote cactus, Lophophora williamsii, is the cactus species appearing to be richest in alkaloids. This Httle spineless sage-green cactus has over the years enjoyed widespread interest, mainly because of its content of the hallucinogenic phenethylamine mescaline, fts natural habitat is northern Mexico and the southern parts of Texas, USA (Anonymous 1959). 

The simple isoquinolines, anhalonidine (12) and anhalamine (13) are bio nthesized in the peyote cactus along with the hallucinogenic phenethylamine, mescaline (6). It is clear, by inspection, that the isoquinoline alkaloids, (12) and (13), are formed from an Ar-C2-N unit like that seen in mescaline (6) with the inclusion of an additional or C2 unit. 

The pathways leading to these bases, which begin in primary metabolism with the a-amino-acid, tyrosine (1) are known in considerable detail. This is the result of quite extensive experiments particularly with various phenethylamine precursors (Lund-strom 1971, Herbert 1980). A key intermediate is 3,4-dihydroxy-5-methoxyphene-thylamine (5) which stands at a fork leading separately to mescaline (6) and the isoquinoline alkaloids methylation at C-3 leads to mescaline (6) whereas methylation at C4 ultimately affords anhalonidine (12) and anhalamine (13) (Fig. 1). The pathways which have been deduced leading to mescaline (6) and to (7) are nicely supported by a Study which explored the specificity of methylation by an O n ethyl transferase isolated from peyote (Basmadjian and Paul 1971, Basmadjian et al. 1978). 

Barton DHR, Cohen T (1957) In Festschrift Dr A Stoll, Birkhauser, Basel, p 117 Barton DHR, Kirby GW, Taylor JB, Thomas GM (1963) Phenol oxidation and biosynthesis, part VI. The biogenesis of amaryllidaceae alkaloids. J Chem Soc 4545—4558 Barton DHR, Hesse RH, Kirby GW (1965) Phenol oxidation and biosynthesis, part VIII. Investigations on the biosynthesis of berberine and protopine. J Chem Soc 6379-6389 Barton DHR, Bracho RD, Potter CJ, Widdowson DA (1974) Phenol oxidation and biosynthesis, part XXIV. Origin of chirality in the erythrinan system and derivation of the lactone rings of a- and ]3-erythroidine. J Chem Soc Perkin Trans 1 2278-2283 Basmadjian GP, Paul AG (1971) The isolation of an O-methyltransferase from peyote and its role in the biosynthesis of mescaline. Uoydia 34 91-93 Basmadjian GP, Hussain SF, Paul AG (1978) Biosynthetic relationships between phenethylamine and tetrahydroisoquinoline alkaloids in peyote. Lloydia 41 375-380 Battersby AR, Binks R, Francis RJ, McCaldin DJ, Ramuz H (1964) Alkaloid biosynthesis, part IV. 1-Benzylisoquinolines as precursors of thebaine, codeine and morphine. J Chem Soc 3600-3610... 

There is considerable variation in structure between the groups of isoquinoline alkaloids, some being simple isoquinolines while others are complex dimers. About 50 simple isoquinolines occur in plants and they are characteristic of some families such as the Cactaceae. Interest in these compounds has stemmed from the well-known hallucinogenic phenethylamine, mescaline, and in one chapter, the occurrence of these simple isoquinolines is reviewed. 

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