THERAPEUTIC POTENTIAL OF SEROTONIN 5-HT3 ANTAGONISTS IN NEUROPSYCHIATRIC DISORDERS

Serotonin 5-HT3-receptors are the only monoamine neurotransmitter receptors that are a member of the ligand-gated ion channel receptor superfamily, enabling these receptors to modulate fast synaptic transmission. Over the past 10 years, 5-HT3-receptors have been extensively investigated. Whilst it is generally accepted that 5-HT3-receptor antagonists attenuate emesis induced by a variety of stimuli, an extensive body of evidence indicates that these ligands may also alleviate some of the symptoms associated with various CNS disorders (e.g. psychosis, anxiety, dementia) and also reduce the rewarding properties of and withdrawal symptoms associated with drugs of abuse. In general, however, the clinical potential described for 5-HT3-receptor antagonists has not been 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 display efficacy in the hands of some experienced investigators, remain major objectives for the future.