Neurotransmitters hallucinogens

The patty drug MDMA (3,4-methylene-dioxymetham-phetamine) as well as amphetamine causes efflux of all monoamine neurotransmitters. The effects of MDMA are described as psychostimulant and hallucinogenic and are judged differently from those of amphetamine. This difference is due to the stronger inhibition of SERT by MDMA as compared with amphetamine, which is a more potent dopamine releaser and moreaddictivethan MDMA. 

For many years it was believed that the brain mechanisms underlying the effects of psychedelic hallucinogens and dissociative anesthetics were separate and distinct. Indeed, there has been considerable debate about which represents the best drag model of schizophrenia. However, recent data show that the two classes of psychotomimetic drags share a common final pathway involving an increase in the release of the excitatory neurotransmitter glutamate. 

Tryptamine itself is found in all major centers of the brain. Its physiologic role in central nervous system (CNS) function, however, remains unclear. 5-Hydroxytryptamine (5-HT, serotonin) is an important neurotransmitter in the CNS. The structural similarity of the tryptamine-related hallucinogens with 5-HT presumably forms the neurochemical basis for their action within the CNS. 

As mentioned herein, other neurotransmitters are affected by hallucinogens. Accordingly, the opposite changes in 5-HT and DA neurotransmission produced by these drugs seem necessary but insufficient to evoke hallucinations. Current studies on the effects of hallucinogens on recently detected neuroactive com-... 

Most studies to date have focused on monoamine systems therefore, it would be of interest to examine the effects of hallucinogenic drugs on the neurochemistry, specific receptor binding, and electrophysiology of other putative neurotransmitter and peptide systems, such as y-aminobutyric acid, glycine, acetylcholine, enkephalin, and substance P. 

The neurotransmitter serotonin (21) has been implicated as playing a role in the mechanism of action of the hallucinogenic indolealkylamines however, the importance of other neurotransmitters cannot be ruled out at this time. Studies targeted specifically toward the elucidation of the mechanism of action of indolealkylamines are considered in other chapters, and this review is limited to a discussion of structure-activity relationships. 

We are still confronted by a list of interesting and important questions that have not been answered. To what extent are dopamine pathways involved in hallucinogenic drug action What is the relative importance of presynaptic versus postsynaptic serotonergic action Is the release of endogenous neurotransmitters... 

Careful analyses of the pharmacologic properties of 3H-hailucinogen binding sites indicated that they may correspond to 5-HT receptors (in the case of 3H-LSD), sigma opiate receptors (in the case of 3H-PCP), or even GABA receptors (in the case of 3H-muscimol). Such data recall that hallucinogens should interfere markedly with the metabolism of neurotransmitters in the CNS. These hallucinogen-induced alterations of neurotransmitter metabolism and functions are summarized below. 

Rech RH, Commissaris RL. (1982). Neurotransmitter basis of the behavioral effects of hallucinogens. Neurosci Biobehav Rev. 6(4) 521-27. 

Psilocybin and psilocin are psychoactive hallucinogenous alkaloids synthesized from the small mushroom genus Psilocybe spp. On average, the concentration of these alkaloids is 300 g in 100 g of mushroom mass. Structurally, these alkaloids are neurotransmitters 5-HT. 

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. 

These drugs seem to act on central 5-HT neurons in a manner that is not clear. They decrease the turnover of serotonin, possibly through a presynaptic receptor in the raphe cells. Since 5-HT is an inhibitory neurotransmitter in many of its actions, the removal of this inhibition could lead to behavioral changes. However, to discredit this simple hypothesis, there are a number of LSD derivatives that are not hallucinogens (e.g., the... 

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