Serotonin 5HT-3 Antagonists

The 5-HT3 receptor is unlike the other serotonin receptors: it is not G protein-coupled but a serotonin-gated, cation-selective ion channel, assembled as a homopentamer or as a heteropentamer with HTR3B, C, D or E, and when activated it causes fast, depolarising responses in neurons. Drugs in this class antagonise that channel. The ondansetron label sets out where that matters: 5-HT3 receptors are present both peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone of the area postrema, and released serotonin may stimulate the vagal afferents through the 5-HT3 receptors and initiate the vomiting reflex; the label adds that it is not certain whether the antiemetic action is mediated centrally, peripherally or at both sites. The class is not uniformly antiemetic - alongside dolasetron, granisetron, ondansetron and palonosetron the cited list also holds trazodone, mirtazapine and vortioxetine, whose principal indications are not antiemetic.