Anti-emetic 5-HT3 antagonists

5-HT3 antagonists

The 5-HT3 receptor is a ligand-gated ion channel which requires serotonin in order to transport Na+ through the membrane. The 5-HT3 antagonists ondansetron and granisetron are other examples of drugs that can control GI motility. However, their most important action is on 5-HT3 receptors present in the vagus nerve, which sends signals directly to the brain's vomiting center in the medulla oblongata, and in the chemoreceptor trigger zone of the brain, which receives "input" from nausea-inducing agents in the bloodstream and communicates with the vomiting centre. By preventing activation of these receptors, 5-HT3 antagonists interrupt one of the pathways that lead to vomiting. It is known that when cytotoxic drugs are used, serotonin is released from enterochromaffin cells causing stimulation of the 5-HT3 receptors. This results in retching, nausea, and vomiting. See also anti-emetics.


In the GI tract, 5-HT3 receptors are located on the vagal sensory neurons and cholinergic neurons. When the 5-HT3 receptor on the vagal sensory neuron is stimulated, it increases the release of acetylcholine which stimulates the chemoreceptor trigger zone (CTZ). When the receptor on the cholinergic receptor is stimulated, it increases muscular contractions (as shown in the figure).

Hence, the 5-HT3 antagonists are commonly used as anti-emetic agents during cytostatic therapy, but their role as anti-motility agents are currently being explored for use in irritable bowel syndrome.


5-HT3 antagonists reduce: