HelixTalk #194 - 5-HT3 Receptor Antagonists for Nausea/Vomiting: An In-Depth Drug Class Review

Date posted: December 5, 2025, 7:05 am

In this episode, we review the pharmacology, indications, adverse effects, and unique drug characteristics of 5-HT3 receptor antagonists such as ondansetron (Zofran) and palonosetron (Aloxi).

Key Concepts

  1. There are four 5-HT3 (serotonin subtype 3) receptor antagonists on the market: ondansetron, granisetron, dolasetron, and palonosetron. These have primarily been studied for acute chemotherapy-induced nausea and vomiting (within 24 hours of chemotherapy administration) and for post-operative nausea and vomiting.
  2. When used for chemotherapy-induced nausea/vomiting, 5-HT3 receptor antagonists are given prior to chemotherapy (usually 30-60 minutes before) on day #1. They are not given on subsequent days because they are not as effective for delayed nausea and vomiting.
  3. Palonosetron has the longest half-life, longer binding affinity to the 5-HT3 receptor, and trends towards having the best efficacy among the 5-HT3 receptor antagonists.
  4. 5-HT3 receptor antagonists are associated with QTc prolongation and may cause headache, dizziness, constipation, or diarrhea. Their association with an increased risk of serotonin syndrome is controversial and not supported from a mechanistic perspective.

References