[Ondansetron--the first highly selective 5-HT3 antagonist in therapy of psychiatric diseases]

Ondansetron is a highly selective 5-HT3 antagonist, which has recently become available for the control of chemotherapy-induced emesis. Since 5-HT3 receptors not only have a high density in the area postrema but also in the hippocampal and amygdala region of the limbic system, it has been suspected that 5-HT3 selective agents have psychotropic effects. In animal models of anxiety ondansetron showed a benzodiazepine-like anxiolytic effect without any sedation or withdrawal effects. Other states of withdrawal have been prevented with ondansetron. This agent might also exert neuroleptic effects since dopaminergic hyperactivity in the mesolimbic system was antagonised by ondansetron. In different models of memory and learning a positive effect on basal learning behaviour and on scopolamine-induced memory impairment was noted. This manuscript reviews essential pharmacological and behavioural effects of ondansetron as well as preliminary data from clinical studies. The role of highly-selective ligands for a more differentiated view of serotonergic subsystems are discussed.