THERAPEUTIC POTENTIAL OF SEROTONIN 5-HT3 ANTAGONISTS IN NEUROPSYCHIATRIC DISORDERS

Serotonin 5-HT3-receptors are the only monoamine neurotransmitter rece ptors that are a member of the ligand-gated ion channel receptor super family, enabling these receptors to modulate fast synaptic transmissio n. Over the past 10 years, 5-HT3-receptors have been extensively inves tigated. Whilst it is generally accepted that 5-HT3-receptor antagonis ts attenuate emesis induced by a variety of stimuli, an extensive body of evidence indicates that these ligands may also alleviate some of t he symptoms associated with various CNS disorders (e.g. psychosis, anx iety, dementia) and also reduce the rewarding properties of and withdr awal symptoms associated with drugs of abuse. In general, however, the clinical potential described for 5-HT3-receptor antagonists has not b een substantiated by a number of preclinical and clinical reports. The further unravelling of the mechanisms underlying the actions of 5-HT3 -receptor antagonists, and the reasons why they apparently fail to dis play efficacy in the hands of some experienced investigators, remain m ajor objectives for the future.