THE CLASSIFICATION OF 5‐HYDROXYTRYPTAMINE RECEPTORS

SUMMARY 1. The current classification of receptors for 5‐hydroxytryptamine (5‐HT) is based on functional studies, and encompasses three main receptor types. 2. 5‐HT 1 ‐like receptors mediate inhibition of release of various neurotransmitters from central and peripheral sites, smooth muscle contraction and relaxation (and release of endothelium‐derived relaxing factor), tachycardia, a variety of behavioural actions (for example, forepaw treading, hypothermia, hyperphagia, drug discriminative stimulus properties, nociceptive pathway modulation, and anxiolytic, anti‐aggressive and prosexual effects), and central neuronal excitatory and inhibitory activity. Selective antagonists for this receptor are not yet available, but the 5‐HT 2 receptor antagonists methysergide and methiothepin have appreciable affinity for 5‐HT 1 ‐like receptors, and 5‐carboxamidotryptamine is a selective agonist. 3. 5‐HT 2 receptors mediate smooth muscle contraction, platelet aggregation, increased capillary permeability, some behavioural syndromes (for example, head twitch and wet‐dog shakes) and drug discriminative stimulus properties, central neuroexcitatory effects, and some neuroendocrine functions. Ketanserin and cypro‐heptadine are selective antagonists. 4. 5‐HT 3 receptors mediate peripheral afferent and efferent neuroexcitatory actions, anxiogenic effects, and modulation of cytotoxic drug‐induced emesis, gastric emptying, and dopamine‐related mesolimbic hyperactivity. Selective antagonists include cocaine, MDL 72222 and ICS 205–930; 2‐methyl‐5‐HT is a selective agonist.