5-HT4 RECEPTORS - POTENTIAL THERAPEUTIC IMPLICATIONS IN NEUROLOGY ANDPSYCHIATRY

Serotonin 5-HT4 receptors were first described in mouse colliculi neur ons. They are positively coupled to adenylyl cyclase, and possess uniq ue pharmacological properties. Indeed, they are not blocked by classic al 5-HT1, 5-HT2 or 5-HT3 antagonists. Several classes of specific 5-HT 4 receptor agonists (benzamides and benzimidazoles) and antagonists ha ve now been described. The most specific and potent 5-HT4 antagonist i s an indole derivative, GR-113808, which has been used to prepare a ra dioligand for 5-HT4 receptors. Both functional and radioligand binding studies indicate that 5-HT4 receptors are expressed in the brain of s everal species, including human brain. The restricted brain distributi on of 5-HT4 receptors indicates that specific neurological and psychia tric functions are affected by these receptors. Thus, specific central nervous system disorders may benefit from the development of 5-HT4 li gands. The similarities between the molecular mechanisms of action of 5-HT4 receptors and those in Aplysia (sea hare) neurons may suggest a role for the receptors in synaptic plasticity events and memory proces ses. The localisation of 5-HT4 receptors in the limbic structures sugg ests a role for the receptors in emotional and reward processes, and e xpression of the receptors in the basal ganglia and substantia nigra i ndicates a role in the control of visuo-motor activity.