Serotonin and hallucinogenic activity

There is abundant experimental evidence to show that serotonin plays a major role in the mechanism of action of hallucinogens, but it is presently unclear whether the actions of hallucinogens can be explained by their agonistic or antagonistic actions. LSD, for example, may behave either as an agonist or antagonist depending on the particular tissue, concentration and experimental condition, whereas the tryptamine type of hallucinogens usually act as agonists. Experimental evidence nevertheless suggests that the behavioural effects of a number of indole alkylamine (e.g. LSD-like) and phenylalkylamine (e.g. mescaline-like) hallucinogens can be attenuated by 5-HT2A antagonists and that the potency of these classes of hallucinogens at 5-HT2A (and possibly 5-HT2c) sites correlate with their hallucinogenic potency in man. It seems unlikely however that all hallucinogens owe their activity to their potency in stimulating 5-HT2A receptors; LSD and 5-methoxydimethyltryptamine for example interact with 5-HT2C sites, while phenyclidine may owe its hallucinogenic potency to an action on N-methyl-D-aspartate (NMDA) and a subclass of sigma receptors. Nevertheless, the balance of evidence suggests that most ''classical'' hallucinogens such as LSD, mescaline and psilocybin act as partial agonists on 5-HT2A receptors.

Details of the pharmacological properties of hallucinogenic drugs are discussed in Chapter 15.

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Defeat Drugs and Live Free

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