The Interactions of the 5-HT3 Receptor with Quipazine-Like Arylpiperazine Ligands. The Journey Track at the End of the First Decade of the Third Millennium

The 5-HT3 receptor (5-HT3R) occupies a special place among the serotonin receptor subtypes because it has been shown to be a ligand-gated ion channel, which is involved in a number of physiological functions and important pathologies. 5-HT3R antagonists have shown an outstanding efficacy in the control of the emesis induced by anticancer chemotherapy and few adverse side-effects, so as to revolutionize the treatment of nausea in cancer patients. This review covers the authors' work performed during the past decade in the development of 5-HT3R ligands belonging to the class of arylpiperazine derivatives related to quipazine (quipazine-like arylpiperazines, QLAs) and represents the extension of the review previously published in Current Topics in Medicinal Chemistry in 2002. The discussion is mainly focused on the most significant structure-affinity relationships emerged in the progress of the work and shows how the original ideas have evolved in the recent years. © 2010 Bentham Science Publishers Ltd.