Mescaline dopamine

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. 

Trulson ME, Crisp T, Henderson U. (1983). Mescaline elicits behavioral effects in cats by an action at both serotonin and dopamine receptors. EurJ Pharmacol. 96(1-2) 151-54. 

A number of very important natural and synthetic biochemicals belong to the phenylethylamine family. Two of these compounds, dopamine and epinephrine (adrenaline), are neurotransmitters, substances that carry chemical messages through the nervous system of humans and other animals. A third phenylethylamine, tyrosine, is an essential amino acid. And a familiar phenylethylamine found in plants is mescaline, whose chemical name is 2-(3,4,5-trimethoxy-phenyl)ethylamine. The primary natural sources of mescaline are four varieties of cactus two peyote species (Lophophora wiUiamsii and Lophophora diffusa), the San Pedro cactus (Trichocereus pacha-noi), and the Peruvian Torch cactus (Trichocereus peruvianus). 

These alkaloids have a phenyl or phenylpropyl nucleus. The group includes simple phenyl amine (tyramine, hordenine), catecholamine (dopamine, noradrenaline, adrenaline), simple tetrahydroisoquinoline (mescaline, anhalamine, anhalonine, anhalonidine), benzylisoquinoline (e.g., papaverine), phthalideiso-quinoline (e.g., noscapine), phenethylisoquinoline (autumnaline, floramultine and kreysigine), tetrahydroisoquinoline (emehne and cephaeline) and terpenoid tetrahydroisoquinoline (secologanin and ipecoside) alkaloids. 

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. 

Morphine and codeine biosynthesis (Samuelsson, 1999 Herbert et al., 2000 Novak et al., 2000) Studies on the biosynthesis of morphine have been carried out mainly on cell cultures mainly of Coptis japonica and species of Thalictrum. Two enzymes (tyrosine decarboxylase and phenolase) catalyze the formation of dopamine from one molecule tyrosine. Dopamine is also the key intermediate in the biosynthesis of mescaline. 

Scheme 27 Biosynthesis of morphine conversion of dopamine to mescaline.

Another naturally occurring drug that is similar to amphetamine can be found in the cactus Lophophora williamsii. Extracts are used to prepare a drink called peyote that contains 3,4,5-trimethoxyphenyl-ethylamine(the meth and phenyl point to a molecule that is quite lipid soluble). Known as mescaline, this compound is structurally similar to the catecholamines dopamine and norepinephrine but seems to act more directly upon serotonin receptors because of the presence of the meth-oxy groups on the molecule. This feature of the compound s structure would make the compound more fat-soluble and therefore better able to enter the brain quickly and may explain... 

The composition of the six controlled substance analogs listed above often stimulate the same areas of the brain, but are chemically quite distinct from one another. MDMA (3, 4-methylenedioxymethampheta-mine) is a complex drug that makes simple classification difficult. Its chemical structure is related both to the stimulant methamphetamine and the hallucinogen mescaline. Methamphetamine bears a close resemblance to two powerful chemicals in the body, dopamine and norepinephrine, which regulate mood, memory, and movement. 

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. 

The biosynthetic work on mescaline in the peyote cactus L. williamsii and in the Peruvian cactus T. pachanoi has led to the formulation of biosynthetic pathways according to Scheme 2. A major pathway probably involves decarboxylation of tyrosine followed by hydroxylation to yield dopamine. Dopamine is methylated on the meta hydroxy group to 4-hydroxy-3-methoxyphenethylamine (3-methoxytyramine) which then undergoes hydroxylation to the key intermediate 4,5-dihydroxy-3-methoxyphenethylamine (20). Para-O-methylation of 20 yields 3,4-dimethoxy-5-hydroxyphenethylamine (21), which is the immediate precursor of the main phenolic tetrahydroisoquinolines of peyote. Alternatively, meta-O-methylation yields 3,5-dimethoxy-4-hydroxyphenethylamine (19), which is further efficiently methylated to mescaline. Parallel pathways involving N-methylated compounds probably exist in these cacti (10). 

MDA-like compounds—such as the TMAs, DOB, DOET, DOM, MMDA, PBR, TMPEA, DMPEA, DMA, PMA and MED A—have molecular structures that resemble mescaline, dopamine and amphetamine. Moreover, the effects are often experienced as being like an interplay between mescaline and amphetamine—one or the other tendency predominating according to the structure of the particular compound. Thus this cluster often has been referred to as "psychedelic amphetamines. (A chemist would probably designate them as "alpha-methyl phenethylamines, "indolealkylamines or "one-ring substituted amphetamines. )... 

Psychedelic drugs (which include lysergide, mescalin, and psilocybin) act primarily by sertonergic mechanisms and indirect effects on dopamine function (2,3). Psilocin is an agonist at 5HT1A and 5HT2a receptors (4). 

Biologically active derivatives of 2-phenylethylamine—adrenaline, noradrenaline, methamphetamine, mescaline, dopamine, fentanyl (a synthetic narcotic), and sumatriptan (Imitrex, a synthetic pain reliever) (Section 25.6C)... 

Aromatic amino acids that originate from the shikimate pathway also act as precursors to many alkaloids. Alkaloids that contain a phenylethylamine moiety are derived from L-tyrosine or its oxidation product L-dihydroxyphenylalanine (L-DOPA). Mescaline (N7) originating from the latter amino acid is known to occur in several cacti and is responsible for the hallucinogenic activity of peyote (Lophophora williamsii, Cactaceae). Lophocerine is a tetrahydroisoquinoline alkaloid derived from L-dopamine and found to occur in a different Lophophora species, L. schotti. 

The. second class of hallucinogens includes MDA and MDMA (ec.stasy), referred to as the methylated amphetamines. As the name suggests, these drugs are structurally related to amphetamine (as is mescaline). MDA and MDMA produce alterations in mood and consciousness with little or no sensory change. They arc thought to act like amphetamine and cocaine on dopamine, norepinephrine, and serotonin synapses (Morton, 2005). 

The exact mechanism of mescaline has not been clearly defined. The central nervous system effects of mescaline appear to involve stimulation of both serotonin and dopamine receptors. In experimental studies, these effects can be blocked by either serotonin antagonists such as methysergide or dopamine antagonists such as haloperidol. Mescaline is structurally related to the amphetamines and cathine (khat). Sympathomimetic effects can occur and are thought to be centrally mediated. Mescaline does not appear to inhibit monoamine oxidase. 

Mescaline causes hallucinogenic effects by stimulating serotonin and dopamine receptors in the central nervous system. The sympathomimetic effects of mescaline are probably also centrally mediated. Changes in catecholamine metabolism and adrenal medullary function may be responsible for the agent s... 

S-methylhomocy teine methionine, methylisogenistin genistein. /V-methylmescaline mescaline, methylmorphine codeine, a-methy I noradrenaline levonordefrin. methyl pentynol (ban. inn] is an acetylenic carbinol. with HYPNOTIC and SEDATIVE properties. It has been used in the treatment of insomnia and as an anxiolytic. methyl-PGEj arbaprostil. methylphenidate [ban, inn] (methylphenidate hydrochloride [jan, usan] Ritalin ) is a CNS STIMULANT and dopamine (re) UPTAKE INHIBITOR. It is used in the treatment of attention-deficit hyperactivity disorder in children, methylphenidate hydrochloride methylphenidate. 

At least eighteen phenylethylamines have been examined by x-ray crystallography. Among these are phenylethylamine hydrochloride (3 ), ephedrine hydrochloride (31), ephedrine monohydrogen phosphate monohydrate (32), ephedrine dihydrogen phosphate (33), dopamine hydrochloride (34), 5-hydroxydopamine hydrochloride (35), 6-hydroxydopamine hydrochloride (36), epinephrine hydrogen tartrate (37), norepinephrine hydrochloride (38), isoproterenol sulfate (39), 2,4,5-trimethoxyamphetamine hydrochloride (40), 4-ethyl-2,5-dimethoxyamphetamine (41), mescaline hydrobromide (42), and mescaline hydrochloride (43). 

---