5-HT3 Antagonist - Mechanism of Action

Mechanism of Action

The 5-HT₃ receptors are present in several critical sites involved in emesis, including vagal afferents, the solitary tract nucleus (STN), and the area postrema itself. Serotonin is released by the enterochromaffin cells of the small intestine in response to chemotherapeutic agents and may stimulate vagal afferents (via 5-HT₃ receptors) to initiate the vomiting reflex. The 5-HT₃ receptor antagonists suppress vomiting and nausea by inhibiting serotonin binding to the 5-HT₃ receptors. The highest concentration of 5-HT₃ receptors in the central nervous system (CNS) are found in the STN and chemoreceptor trigger zone (CTZ), and 5-HT₃ antagonists may also suppress vomiting and nausea by acting at these sites.

When patients undergo chemotherapy, serotonin is released from enterochromaffin cells by the cytotoxicity, the selective 5-HT₃ receptor antagonists prevent the ability of serotonin to activate and sensitize gastrointestinal vagal-nerve terminals to other emetogenic substances released.