Section Review—Central & Peripheral Nervous Systems: 5-HT₃ Receptor Antagonists in Development As-Anxiolytics

Abstract

Different serotonin (5-HT) receptor subtypes are targets for drugs of actual or potential interest in psychiatry. Among them, 5-HT₃ receptors may be of considerable interest in the development of new psychotropic drugs. Many 5-HT₃ receptor antagonists show an anxiolytic-like activity at very low doses in different models of anxiety, particularly in the light-dark test in mice. Conflicting results have been reported in other animal models such as the elevated plus-maze in rats or in conflict procedures. In general, the dose-response curve for the anxiolytic effect of 5-HT₃ receptor antagonists is bell-shaped and these compounds lose efficacy at high doses. Experimental studies suggest that 5-HT₃ antagonists offer some advantages over benzodiazepines such as apparent lack of tolerance and dependence, minimal or null effects of psychomotor performance and not only do not induce amnesia but may also enhance memory consolidation. Although few clinical studies have been published so far with 5-HT₃ receptor antagonists, these studies appear to suggest efficacy and quick onset of action in the treatment of generalised anxiety disorders. Further clinical investigation is nc doubt necessary until some obvious advantage of this class of compounds over benzodiazepines in some subgroup of human anxiety disorders is recognised.