Proposals for the classification and nomenclature of functional receptors for 5-hydroxytryptamine

Abstract As a result of controversy in the literature regarding the classification and nomenclature of functional receptors for 5-hydroxytryptamine (5-HT), a framework for classification is proposed. The formulation of these proposals has only been made possible by the recent advent of new drug tools. It is considered that there are three main types of 5-HT receptor, two of which have been well characterised pharmacologically, using selective antagonists, and which it is proposed to name 5-HT 2 and 5-HT 3 . These two groups broadly encompass the “D” and “M” receptors, respectively, which Gaddum identified in the guinea-pig ileum (Gaddum and Picarelli, 1957). The 5-HT 2 receptor, which mediates a variety of actions of 5-HT, has been definitively shown to correlate with the 5-HT 2 binding site in the brain. No binding studies in brain tissue have yet been published with radiolabelled ligands specific for 5-HT 3 receptors. A number of other actions of 5-HT appear to be mediated via receptors distinct from 5-HT 2 or 5-HT 3 receptors. Since selective antagonists are not yet available, these receptors cannot be definitively characterised, although in many cases they do have some similarities with 5-HT 1 binding sites, which are a heterogeneous entity. Criteria are proposed for tentatively classifying these receptors as “5-HT 1 -like” (Table 1). Definitive characterisation of these receptors will await the identification of specific antagonists. This classification of 5-HT receptors into three main groups (Table 1) is based largely, but not exclusively, on data from studies in isolated peripheral tissues where definitive classification is possible. However, it is believed that this working classification will be relevant to functional responses to 5-HT in the central nervous system.