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[Pharmacology](https://durgical.com/en/pharmacology/) · Class

# NK1 receptor antagonists

Antiemetics that block substance P at brain NK1 receptors. Added to a setron and dexamethasone, they prevent both acute and delayed chemotherapy vomiting.

Updated 2026-11-01

## What they are

Aprepitant (oral) and its intravenous prodrug fosaprepitant are used with a 5-HT3 antagonist and dexamethasone to prevent nausea and vomiting from highly and moderately emetogenic chemotherapy. They are for prevention, not for vomiting that has already started.

## Mechanism of action

Substance P is a neuropeptide released in the brainstem vomiting circuits (nucleus of the solitary tract, area postrema) after emetogenic chemotherapy; it acts on neurokinin-1 (NK1) receptors, Gq-coupled receptors, and drives above all the delayed phase of vomiting. NK1 antagonists cross the blood–brain barrier, occupy brain NK1 receptors and block that signal. They have little affinity for serotonin, dopamine or corticosteroid receptors, so they add to the effect of setrons and dexamethasone.

Target: Tachykinin NK1 receptor (substance P receptor)

## Key points

- They target delayed chemotherapy-induced vomiting, which setrons control poorly; the classic triple is NK1 antagonist + 5-HT3 antagonist + dexamethasone.
- Aprepitant inhibits and induces CYP3A4: the dexamethasone dose is reduced when they are combined, and pimozide is contraindicated.
- Aprepitant lowers the INR of patients on warfarin and reduces the efficacy of hormonal contraceptives during and for about a month after treatment.
- Fosaprepitant is an intravenous prodrug converted to aprepitant; it can cause infusion-site reactions and hypersensitivity, including anaphylaxis.

## Drugs in this class

- [**Aprepitant** An oral NK1 blocker that prevents acute and delayed vomiting from chemotherapy, given with a setron and dexamethasone… Tachykinin receptor 1 (NK1, substance P receptor)](https://durgical.com/en/pharmacology/aprepitant/)
- [**Fosaprepitant** The intravenous prodrug of aprepitant, given before chemotherapy to prevent vomiting. It can irritate the vein and is… Tachykinin receptor 1 (NK1, substance P receptor)](https://durgical.com/en/pharmacology/fosaprepitant/)

## Others in the class

- Rolapitant
- Netupitant (combined with palonosetron)

## Test yourself

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

## Which phase of chemotherapy-induced vomiting do NK1 antagonists add most to?

The delayed phase, driven mainly by substance P, which setrons alone control poorly.

## Why is the dexamethasone dose reduced when it is given with aprepitant?

Aprepitant inhibits CYP3A4, which metabolises dexamethasone, so dexamethasone levels rise.

## What should a woman on hormonal contraception know when she receives aprepitant?

Its efficacy can fall during treatment and for about a month after; a back-up method is used.

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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 - APREPITANT capsule APREPITANT kit](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d72e0e10-4557-41b0-b65d-d395468cad19) (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=A04AD) (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Source: https://durgical.com/en/pharmacology/classes/nk1-receptor-antagonists/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/classes/nk1-receptor-antagonists/