Classification of serotonin receptors.

The subdivision of serotonin (5-HT) receptors into three classes, designated 5-HT1, 5-HT2, and 5-HT3, has been based on radioligand binding studies and experiments in isolated tissues. As a result of radioligand binding studies, two types of 5-HT recognition sites have been postulated. One site specifically labeled by [3H]5-HT was termed 5-HT1, and the other one labeled by [3H]spiperone or [3H]ketanserin was designated 5-HT2. The pharmacological properties of the latter sites are obviously identical to those of the majority of the classical "D" receptors, whereas a smaller proportion of "D" receptors resemble the 5-HT1 type. Hence, according to the current definition, 5-HT1 and 5-HT2 receptors mediate effects previously ascribed to "D" receptors. Three subtypes of 5-HT1 binding sites, designated 5-HT1A, 5-HT1B, and 5-HT1C, can now be distinguished by improved binding assay with rather selective radioligands. The identity of a given 5-HT binding site with a 5-HT receptor was suggested by correlating the agonists' and antagonists' affinities for the binding site with their potencies to produce certain effects. This was further confirmed by the development of rather selective agonists and antagonists. A third class of 5-HT receptors, the "M" receptors, which are now designated 5-HT3 in order to distinguish them from muscarinic cholinoceptors, were identified in functional in vitro experiments. They are present on terminals of sympathetic and parasympathetic nerves and on afferent nerve fibers. All three receptor classes are involved in cardiovascular regulation.