The 5-HT<sub>3</sub> receptor as a therapeutic target

^{University of Cambridge, Department of Biochemistry, Tennis Court Road, Cambridge , CB2 1QW, UK}

^{Author for correspondence University of Cambridge, Department of Biochemistry, Tennis Court Road, Cambridge, CB2 1QW, UK Tel: +441223 765950; Fax: +441223 333345; E-mail:}ku.ca.mac@021lS

Abstract

The 5-HT₃ receptor is a neurotransmitter-gated ion channel. It is a member of the Cys-loop family of receptors, which also includes nicotinic acetylcholine, glycine and GABA_A receptors. Each member of the family consists of an arrangement of five subunits surrounding a central ion-conducting pore. The 5-HT₃ receptor binding site is composed of six loops from two adjacent subunits, and the critical ligand binding residues within these loops are well documented. There are a range of 5-HT₃ receptor agonists and competitive antagonists, but it is the antagonists that dominate their clinical use. Studies have proposed a range of disease symptoms that might be amenable to 5-HT₃ receptor selective compounds; however, so far only the treatment of emesis and irritable bowel syndrome have been fully realised. In this review, the authors look at the structure, function and distribution of 5-HT₃ receptors and how this may influence their role in disease. The authors also describe the existing clinical applications of 5-HT₃ antagonists and the future potential of these drugs.

Keywords: 5-HT₃, alosetron, Cys-loop receptor, dolasetron, emesis, granisetron, irritable bowel syndrome, ondansetron, palonosetron, ramosetron, tropisetron

Abstract

Bibliography

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