R.M. Eglen* and D.W. Bonhaus Pages 367 - 374 ( 8 )
The 5-HT3 receptor is unique among known monoamine receptors in that, rather than being a G protein-coupled receptor, it forms a ligand-gated ion channel. In the CNS, this receptor is found in high density in· nuclei of the lower brainstem, area postrema and nucleus of the tractus solitarius. Lower densities of the receptor are found in the cerebral cortex and limbic areas, including the hippocampus. In the periphery, 5-HT3 receptors are located on pre- and postganglionic neurons of both sensory and enteric nervous systems. The receptor is a pentameric protein with multiple agonist and allosteric ligand binding sites. Thus it has structural and functional similarities with nicotinic, GABAergic and, other ligand gated ion channels.
5-HT3 receptor antagonists have been shown to produce beneficial effects in animal models of cognitive and psychiatric disorders. Whether 5-HT3 receptor antagonists may have similar profound effects in the treatment of anxiety, depression or psychosis will be determined by the outcome of ongoing clinical trials. However, it is in the treatment of cancer chemotherapy induced emesis that 5-HT3 receptor antagonists have had their·greatest impact. The cytotoxic agents used in cancer chemotherapy provoke the release of 5-HT from enterochromaffin cells in the gastrointestinal tract. This 5-HT acts on 5-HT3 receptors in the central nervous system or on peripheral vagal afferent fibers to initiate vomit reflexes. 5-HT3 receptor antagonists block this action and thereby greatly reduce the number of emetic episodes that occur during cancer chemotherapy. The marked clinical efficacy of 5-HT3 receptor antagonists such as ondansetron, granisetron and tropisetron together with their lack of adverse side effects has revolutionized the treatment of cancer chemotherapy induced emesis.