Pharmacology · Dopamine-antagonist antiemetics and prokinetics

Domperidone !

A D2 blocker that relieves nausea and speeds the stomach while barely entering the brain. Its risk is the heart: QT prolongation and arrhythmias.

Updated 2026-11-01

Class: Dopamine-antagonist antiemetics and prokinetics
Receptor: Dopamine D2 receptor
ATC code: A03FA03

Dopamine D2 receptorDomperidone

No structure of domperidone bound to D2 exists; the figure shows haloperidol in the same dopamine pocket of the human D2 receptor.

Target in 3D: Dopamine D2 receptor. PDB structure 6LUQ (RCSB PDB, public domain). View the structure at RCSB PDB

Mechanism of action

Domperidone blocks dopamine D2 receptors with little action on other receptors. In the stomach it removes dopamine's brake on acetylcholine release from enteric neurons, so gastric emptying speeds up. It does not readily cross the blood–brain barrier, but it reaches the parts of the brain that lie outside it: the chemoreceptor trigger zone (less nausea), the pituitary (more prolactin) and the temperature centre. This is why it causes few extrapyramidal effects compared with metoclopramide.

Blocks D2 receptors in the gut and the chemoreceptor trigger zone
More acetylcholine release speeds gastric emptying
It barely crosses the blood–brain barrier: few extrapyramidal effects
Pituitary D2 block raises prolactin

Pharmacokinetics

Absorption: Rapidly absorbed by mouth; peak levels in about half an hour.
Metabolism: Liver, by CYP3A4 (N-dealkylation and hydroxylation); CYP3A4 inhibitors raise its levels.
Elimination: Metabolites leave about two-thirds in the faeces and one-third in the urine.
Half-life: About 7 hours.

Indications

Relief of nausea and vomiting (in the EU, restricted to this use, at low doses and for short courses).
Gastroparesis, where it is available. Gastroparesis (delayed gastric emptying) →

Adverse effects

Common

Raised prolactin: galactorrhoea, gynaecomastia, amenorrhoea, impotence

Contraindications

Moderate or severe liver impairment
Conditions that impair cardiac conduction, or underlying heart disease such as heart failure
Use with QT-prolonging drugs or potent CYP3A4 inhibitors

Key interactions

Potent CYP3A4 inhibitors: Less breakdown of domperidone, higher levels and more arrhythmia risk; the combination is contraindicated.
Other QT-prolonging drugs: Additive QT prolongation; the combination is contraindicated.

What is monitored

ECG and electrolytes in patients with cardiac risk
Duration of treatment, which is kept short
Breast symptoms or menstrual changes (prolactin)

Administration and safety

Oral or rectal; the injectable form was withdrawn in 1985 because of cardiac effects
Used at the lowest effective dose for the shortest time, usually no more than a week
Medication lists are checked for QT-prolonging drugs and CYP3A4 inhibitors before starting

Nursing care

Ask about heart disease, fainting and palpitations before the first dose
Review the medication list for drugs that prolong QT or inhibit CYP3A4
Teach the patient to report palpitations or fainting at once
Explain that treatment is short

Pregnancy and breastfeeding

Data are limited; the risk is weighed against the benefit by the treating doctor.

Test yourself

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

Why does domperidone cause fewer extrapyramidal effects than metoclopramide?

It does not readily cross the blood–brain barrier, so it barely reaches the basal ganglia.

How can domperidone act on the chemoreceptor trigger zone if it barely enters the brain?

The trigger zone in the area postrema lies outside the blood–brain barrier.

Which serious risk led the EU to restrict domperidone to short, low-dose use for nausea and vomiting?

Cardiac risk: QT prolongation, serious ventricular arrhythmias and sudden cardiac death.

Add to my cards (3)

Gastroparesis (delayed gastric emptying)

← Back to the class: Dopamine-antagonist antiemetics and prokinetics

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

Sources: Domperidone-containing medicines - referral | European Medicines Agency (EMA) (European Medicines Agency (EMA), 2014); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 54 (McGraw Hill, 2023); RCSB PDB - 6LUQ: Haloperidol bound D2 dopamine receptor structure inspired discovery of subtype selective ligands (RCSB Protein Data Bank, 2026).

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Representative model, for educational purposes only.