The 5-HT3 receptor as a therapeutic target.
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 GABAA 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.
Thompson
Andrew J
AJ
University of Cambridge, Department of Biochemistry, Tennis Court Road, Cambridge, CB2 1QW, UK.
Lummis
Sarah C R
SC
D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation; D044406:Receptors, Serotonin, 5-HT3 / Q000737:chemistry / Q000378:metabolism*; D058831:Serotonin 5-HT3 Receptor Antagonists; D012702:Serotonin Antagonists / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*
D044406:Receptors, Serotonin, 5-HT3; D058831:Serotonin 5-HT3 Receptor Antagonists; D012702:Serotonin Antagonists