Mescaline structure

The natural prototype for the phenylalkylamines is mescaline (Structure 1), isolated from the peyote cactus (Lophophora williamsii) by Heffter in 1896 (100) and subsequently obtained synthetically by Spath in 1919 (218). Used for many centuries in the form of peyote by Indians in Mexico and the American Southwest (3), it is often referred to as one of the classic hallucinogens, along with psilocybin, psilocin, and LSD. Little structure-activity work was directed toward mescaline or its congeners until 1955, when Peretz et al. (174) reported that a-methyl mescaline (TMA) (8), which represented a hybrid of the structure... 

Mescaline a hallucinogenic amine obtained from the peyote cactus has been synthesized in two steps from 3 4 5 trimethoxybenzyl bromide The first step is nucleophilic substitution by sodium cyanide The second step is a lithium aluminum hydnde reduction What is the structure of mescaline" ... 

The phenylalkylamine hallucinogens show a close structural resemblance to the catecholamines, noradrenahne and dopamine. The prototype structure is found in mescaline, a naturally occurring substance. Modification of the mescaline molecule has led to synthetic amphetamine derivatives with hallucinogenic action. 

Recent controversy about the recreational abuse and potential therapeutic use of designer drugs has focused attention on MDA (methylenedioxyampheta-mine HCl) and structurally related phenylisopropylamine compounds, including MDMA istructural analogs of the psychomotor stimulant amphetamine and the hallucinogen mescaline, and produce stimulant and/or hallucinogenic effects (Shulgin 1978). 

Smythies, J. R., and Sykes, E. A. (1966) Structure-activity relationship studies on mescaline The effect of dimethoxyphenylethylamine and N N-dimethyl mescaline on the conditioned avoidance response in rat. Psychopharmacologia, 8 324-330. 

Seven groups of these drugs can be separated based on their various chemical f structures (a) lysergic acid derivatives, of which lysergide (LSD) is the prototype (b) phenylethylamine derivatives, of which 3,4,5-trihydroxyphenylethylamine (mescaline) is the prototype (c) indolealkylamines, such as 4-phosphorodi-methyltryptamine (psilocybin) (d) other indolic derivatives, such as the harmine... 

For the purposes of this chapter, hallucinogens are divided into two separate categories. The first section covers the substituted phenylalkylamines, with the prototype for these structures being mescaline. The second category includes indole-based compounds, including various substituted tryptamines, beta-car-bolines, and LSD. 

While mescaline is a simple 2-phenethylamine derivative, the addition of an alpha-methyl group to the side chain yields Structure 8 (TMA). This simple hybrid of the structures of mescaline and amphetamine retains the hallucinogenic effects of mescaline but possesses about twice the potency of the latter (174,200). Addition of the alpha-methyl to other 3,4,5-substituted compounds generally brings about an approximately twofold increase in potency. The addition of an alpha-methyl to 2,4,5-substituted compounds, however, may dramatically increase activity. For example, 2-(2,4,5-trimethoxyphenyl) ethylamine apparently is clinically inactive (195). Addition of an alpha-methyl gives TMA-2 (Table 1), with 20 times the potency of mescaline. However, the addition of an alpha-methyl does not significantly increase in vitro receptor affinity in either 3,4,5-or 2,4,5-series (72,78). Thus it is probable that the alpha-methyl may confer metabolic stability in vivo. It could also be speculated that this protection is more important in the 2,4,5-substituted series than in 3,4,5-substituted compounds. 

Phenethylamine is structurally related to a number of psychedelics, including mescaline. It also occurs in chocolate and is thought to be one of the substances responsible for the feel good effect of chocolate (other molecules contribute as well, including theobromine). Chocoholics will understand. 

The transmethylation hypothesis depended on the psychosis of mescaline as an example of how methylated compounds similar in structure to the monoamine neurotransmitters could be psychotogenic, and demonstrated how methionine, the precursor of the methyl donor S-adenosylmethionine, could exacerbate the psychotic symptoms of schizophrenia in patients. This theory was fed by studies of the now notorious pink spot, an amine found in paper chromatography of urine extracts from schizophrenics and thought to be 3,4-dimethoxyphenylethylamine (i.e., O-methylated dopamine). Subsequent studies eventually identified this as another compound or compounds, primarily of dietary origin. Another methylated derivative erroneously proposed to be found in higher quantities in schizophrenia was dimethyltryptamine. This compound is similar in structure to LSD, the hallucinogenic nature of which was the key to the serotonin deficiency hypothesis, which proposed that the known antagonism of serotonin (5-HT) by LSD indicated that psychotic disorders such as schizophrenia may result from a hypofunction of 5-HT. 

The hallucinogens generally fall into two chemical classes. The indole alkylamines include LSD, psilocybin, psilocin, dimethyltryptamine (DMT), and diethyltrypta-mine (DET), all of which are structurally similar to serotonin. The other chemical subclass of hallucinogens contains phenylethylamine derivatives such as mescaline, MDMA, MDA, and DOM (dimethoxymethyl amphetamine). A related stimulatory hallucinogen, PCP, is a piperidine analogue that produces unique effects. 

An alkaloid is a complex organic chemical substance found in plants, which characteristically combines nitrogen with other elements, has a bitter taste, and typically has some toxic, stimulant, analgesic effects. There are many different alkaloids, 30 of which are found in the opium plant. While morphine is the most important alkaloid in opium—for its natural narcotic qualities as well as providing the chemical structure for heroin—another alkaloid, codeine, is also sought after for its medicinal attributes. Other alkaloids include papaverine, narcotine, nicotine, atropine, cocaine, and mescaline. While the concentration of morphine in opium varies depending on where and how the plant is cultivated, it typically ranges from 3 percent to 20 percent. 

Cross tolerance has been demonstrated between LSD and mescaline, psilocybin, and psilocin. There seems to be no cross tolerance between LSD and marijuana or amphetamine. These observations are indicative of the structural similarites of the compounds. 

The emotions mescaline evokes are not always pleasant. Although one may feel euphoria and a sense of cosmic transcendence, one may also see grotesque faces and have a gripping sense of terror. By this time, the brain effects have spread far beyond the visual system. More specifically, they have by now clearly engaged those limbic structures that constituted Kliiver s second scientific focus of interest. 

QUALITATIVE COMMENTS (with]35mg) I had no nausea, although I always vomit with mescaline. Somehow my personality was divided and exposed, and this allowed me to understand my psychic structure more clearly. But maybe others could look in there, too. The psychiatric use of this drug would be interesting to pursue. It is not completely pleasant, maybe because of this personal intimacy. ... 

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