What is the mechanism of action of Ondansetron?

From the Guidelines

Ondansetron works by blocking serotonin (5-HT3) receptors in the brain and gut, preventing nausea and vomiting by inhibiting these receptors in the chemoreceptor trigger zone of the brain and in the gastrointestinal tract. This mechanism of action is crucial in preventing chemotherapy-induced nausea and vomiting, as well as nausea and vomiting caused by other conditions such as radiation and surgery 1.

Key Points About Ondansetron's Mechanism of Action

• Ondansetron competitively blocks 5-HT3 receptors, preventing serotonin from binding and thus stopping the signal that would otherwise lead to nausea and vomiting.
• The medication is effective for chemotherapy-induced, radiation-induced, and postoperative nausea and vomiting.
• It has a rapid onset of action, typically within 30 minutes, making it a valuable option for patients experiencing acute nausea and vomiting.

Administration and Dosage

• Ondansetron can be administered orally or intravenously, with typical doses ranging from 4-8 mg every 8-12 hours for adults.
• The specific dosage and administration schedule may vary depending on the indication and patient factors, such as age and renal function.

Side Effects and Considerations

• Common side effects of ondansetron include headache, constipation, and rarely QT interval prolongation on ECG.
• Despite these potential side effects, ondansetron remains a highly effective and widely used antiemetic medication, particularly in the context of chemotherapy-induced nausea and vomiting 1.

From the FDA Drug Label

Ondansetron is a selective 5-HT 3receptor antagonist. While its mechanism of action has not been fully characterized, ondansetron is not a dopamine-receptor antagonist. Serotonin receptors of the 5-HT 3type are present both peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone of the area postrema It is not certain whether ondansetron’s antiemetic action is mediated centrally, peripherally, or in both sites. However, cytotoxic chemotherapy appears to be associated with release of serotonin from the enterochromaffin cells of the small intestine. In humans, urinary 5-hydroxyindoleacetic acid (5-HIAA) excretion increases after cisplatin administration in parallel with the onset of emesis The released serotonin may stimulate the vagal afferents through the 5-HT 3receptors and initiate the vomiting reflex.

The mechanism of action of Ondansetron is as a selective 5-HT3 receptor antagonist. It works by blocking the action of serotonin at the 5-HT3 receptors, which are found in the vagal nerve terminals and the chemoreceptor trigger zone of the area postrema. This blocking action prevents the initiation of the vomiting reflex, which is associated with the release of serotonin from the enterochromaffin cells of the small intestine during cytotoxic chemotherapy. The exact site of action (central, peripheral, or both) is not fully characterized 2.

• Key points:
  • Selective 5-HT3 receptor antagonist
  • Blocks serotonin action at 5-HT3 receptors
  • Prevents vomiting reflex initiation
  • Exact site of action not fully characterized 2

From the Research

Mechanism of Action of Ondansetron

• Ondansetron is a potent and highly selective 5-HT3 receptor antagonist that prevents emesis following chemotherapy by antagonising the action of 5-hydroxytryptamine (5-HT) at 5-HT3 receptors on vagal afferent neurons that innervate the gastrointestinal tract and 5-HT3 receptors in the central vomiting system 3.
• The mechanism of action of ondansetron involves blocking the initiation of the emetic reflex by preventing the activation of 5-HT3 receptors at two sites: centrally, in the area postrema and nucleus tractus solitarius, and peripherally, on vagus nerve terminals 4.
• Ondansetron's anti-emetic activity is thought to be due to its selective inhibition of 5-HT3 receptors, which are located in the chemoreceptor trigger zone and the gastrointestinal tract 5, 6, 7.
• The drug's ability to block 5-HT3 receptors in the area postrema and on vagus nerve terminals prevents the stimulation of vagal afferent nerves and the subsequent activation of the central vomiting system, thereby preventing emesis 3, 4.

Sites of Action

• Central: area postrema, nucleus tractus solitarius (NTS) 4
• Peripheral: vagus nerve terminals 4
• Chemoreceptor trigger zone in the area postrema 5, 7
• Gastrointestinal tract 3, 6, 7

Key Findings

• Ondansetron is a highly potent and selective antagonist at 5-HT3 receptors 3, 4.
• The drug's anti-emetic activity is very powerful in preventing nausea and vomiting induced by chemotherapy 7.
• Ondansetron has been shown to be effective in controlling nausea and vomiting in patients treated with cisplatin and other emetogenic chemotherapy agents 5, 6.