Serotonin receptor 3 (5-HT3)

Serotonin receptor 3 (5‑HT₃) is a member of the Cys-loop family of ligand-gated ion channels that mediates fast excitatory neurotransmission in both central and peripheral nervous systems. Unlike most other serotonin receptors—which are G protein-coupled—5‑HT₃ forms a pentameric structure surrounding a central cation-selective pore. Functional receptors can be homopentamers composed solely of the A subunit or heteropentamers including B–E subunits; only those containing at least one A subunit are functional. Activation by serotonin leads to rapid membrane depolarization via sodium and potassium influx, triggering neuronal excitation and neurotransmitter release. The primary clinical significance lies in its role as a therapeutic target for antiemetic drugs used to prevent nausea/vomiting associated with chemotherapy or surgery; it also plays roles in pain perception, anxiety regulation, gut motility modulation, and possibly neurodevelopmental processes.[1][2][4]

Other names

5-HT3 receptor5-hydroxytryptamine receptor 3HTR3Htr3a (for the A subunit)Serotonin-gated ion channel receptor5HT3 serotonin receptorSerotonin receptor 3A (for the A subunit)5HT3A[7]

Antagonists block serotonin binding to the receptor, preventing cation influx, neuronal depolarization, and subsequent neurotransmitter release—this underlies their antiemetic effect. Agonists activate the cation-selective ion channel, leading to rapid neuronal excitation.[1][9]