Therapeutics of 5-HT₃ receptor antagonists: Current uses and future directions

The 5-Hydroxytryptamine₃ (5-HT₃) receptor is a member of the cys-loop family of ligand gated ion channels, of which the nicotinic acetylcholine receptor is the prototype. All other 5-HT receptors identified to date are metabotropic receptors. The 5-HT₃ receptor is present in the central and peripheral nervous systems, as well as a number of non-nervous tissues. As an ion channel that is permeable to the cations, Na⁺, K⁺, and Ca²⁺, the 5-HT₃ receptor mediates fast depolarizing responses in pre- and post-synaptic neurons. As such, 5-HT ₃ receptor antagonists that are used clinically block afferent and efferent synaptic transmission. The most well established physiological roles of the 5-HT₃ receptor are to coordinate emesis and regulate gastrointestinal motility. Currently marketed 5-HT₃ receptor antagonists are indicated for the treatment of chemotherapy, radiation, and anesthesia-induced nausea and vomiting, as well as irritable bowel syndrome. Other therapeutic uses that have been explored include pain and drug addiction. The 5-HT₃ receptor is one of a number of receptors that play a role in mediating nausea and vomiting, and as such, 5-HT₃ receptor antagonists demonstrate the greatest anti-emetic efficacy when administered in combination with other drug classes.