Identification and classification of 5-HT1 receptor subtypes.

Serotonin (5-HT) plays a major role as a neurotransmitter in the brain and large amounts are found in blood platelets. 5-HT release can be induced by action potentials invading the nerve terminals and by platelet aggregation. The targets of 5-HT are specific receptors mediating a wide variety of central and peripheral effects. For two of the main 5-HT receptor classes, the 5-HT2 and 5-HT3 receptors, selective antagonists are available, but this is not the case for the heterogeneous population of 5-HT1 receptors. In addition, the drugs with antagonistic properties at the 5-HT1A, 5-HT1B, 5-HT1C, and 5-HT1D receptors block other 5-HT receptors or even entirely different receptors (e.g., beta-adrenoceptors); as a rule, they do not discriminate between the four 5-HT receptor subtypes. Identification and characterization of these subtypes is further complicated by the fact that, with the exception of drugs activating 5-HT1A receptors, e.g., 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and urapidil; no subtype-selective agonists are available. Hence, the pharmacological characterization of a 5-HT1 receptor must be based on experiments with several putative 5-HT receptor agonists and antagonists with an overlapping profile of affinities for the various 5-HT1 receptor subclasses. The 5-HT1A receptor is the best-defined subclass and has already been cloned. It has been identified on cell bodies of 5-HT neurons in the raphe nuclei, and it mediates inhibition of cell firing.(ABSTRACT TRUNCATED AT 250 WORDS)