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# 5-HT3 receptor antagonists (setrons)

Antiemetics that block serotonin's 5-HT3 receptor on gut nerves and in the brainstem. First line for chemotherapy and post-operative vomiting.

Updated 2026-11-01

## What they are

The «setrons» (ondansetron, granisetron, palonosetron, tropisetron) prevent and treat nausea and vomiting after chemotherapy, radiotherapy and surgery. They do not block dopamine, so they cause no extrapyramidal effects.

## Mechanism of action

Chemotherapy and radiation damage the enterochromaffin cells of the gut lining, which release serotonin. Serotonin opens 5-HT3 receptors, ligand-gated cation channels on vagal afferent nerves, and the signal travels to the nucleus of the solitary tract and the area postrema (chemoreceptor trigger zone) in the brainstem. Setrons sit in the serotonin-binding pocket between two subunits of the receptor and keep the channel closed, so the vomiting reflex is not triggered.

Target: Serotonin 5-HT3 receptor (ligand-gated ion channel)

## Key points

- They block 5-HT3, a ligand-gated ion channel, not a G-protein-coupled receptor: it is the only ion-channel serotonin receptor.
- They work best on acute chemotherapy-induced vomiting; they are combined with dexamethasone and, for highly emetogenic regimens, with an NK1 antagonist.
- QT prolongation is the class's key cardiac risk: ondansetron prolongs QT in a dose-dependent way and torsades de pointes has been reported.
- Constipation and headache are the most common adverse effects; serotonin syndrome can occur with SSRIs, SNRIs and other serotonergic drugs.
- Palonosetron is the long-acting member of the class.

## Drugs in this class

- [**Ondansetron** The most used setron: blocks serotonin 5-HT3 receptors to prevent vomiting after chemotherapy and surgery. Its key… Serotonin 5-HT3A receptor](https://durgical.com/en/pharmacology/ondansetron/)
- [**Granisetron** A 5-HT3 antagonist like ondansetron, used before chemotherapy, radiotherapy and surgery to prevent vomiting… Serotonin 5-HT3A receptor](https://durgical.com/en/pharmacology/granisetron/)
- [**Palonosetron** A long-acting 5-HT3 antagonist given by IV before chemotherapy. Its half-life of about 40 hours also covers the… Serotonin 5-HT3A receptor](https://durgical.com/en/pharmacology/palonosetron/)

## Others in the class

- Dolasetron
- Ramosetron

## Test yourself

Think of the answer, then tap the question to see it.

## What kind of receptor is the 5-HT3 receptor?

A ligand-gated cation channel (a pentameric ion channel), unlike the other serotonin receptors, which are G-protein-coupled.

## Where do 5-HT3 antagonists act to stop chemotherapy-induced vomiting?

On 5-HT3 receptors of vagal afferent nerves in the gut and in the brainstem (area postrema and nucleus of the solitary tract).

## Why do setrons not cause dystonia or tardive dyskinesia?

They do not block dopamine D2 receptors, which is what causes the extrapyramidal effects of metoclopramide and the phenothiazines.

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: [DailyMed - ONDANSETRON injection](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=60d09eb8-40e8-48f8-bbbf-70ba701754e2) (DailyMed (U.S. National Library of Medicine), 2026); [Nausea and Vomiting - Gastroenterology - MSD Manual Professional Edition](https://www.msdmanuals.com/professional/gastrointestinal-disorders/symptoms-of-gastrointestinal-disorders/nausea-and-vomiting) (MSD Manual Professional Edition, 2025); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=A04AA) (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/classes/5-ht3-receptor-antagonists/