Pharmacology · Dopamine-antagonist antiemetics and prokinetics
Metoclopramide !
A D2 blocker that stops nausea and speeds up the stomach. Long or heavy use can cause tardive dyskinesia, a movement disorder that may be permanent.
Updated 2026-11-01
No structure of metoclopramide bound to D2 exists; the figure shows haloperidol in the human D2 receptor, in the same orthosteric dopamine pocket that metoclopramide blocks.
Mechanism of action
Metoclopramide blocks dopamine D2 receptors in the chemoreceptor trigger zone of the area postrema, which lowers nausea and vomiting. In the upper gut it removes dopamine's brake on motility, stimulates 5-HT4 receptors on enteric neurons and makes the muscle more responsive to acetylcholine: antral contractions grow stronger, the pylorus and duodenal bulb relax and the lower oesophageal sphincter tightens, so the stomach empties faster. The colon is hardly affected. Because it enters the brain, it also blocks D2 receptors in the basal ganglia (extrapyramidal effects) and the pituitary (more prolactin).
- Blocks D2 receptors in the chemoreceptor trigger zone: less nausea
- Lifts dopamine's brake and boosts acetylcholine's effect on gut muscle
- Stronger antral contractions and a relaxed pylorus empty the stomach
- D2 block in the basal ganglia explains dystonia and tardive dyskinesia
Pharmacokinetics
- Absorption
- Well absorbed by mouth, about 80% bioavailable; also given IV and IM.
- Distribution
- Wide distribution into tissues; only about 30% bound to plasma proteins; crosses the placenta and into breast milk.
- Metabolism
- Partly in the liver, with CYP2D6 involved; poor CYP2D6 metabolisers clear it more slowly.
- Elimination
- Mainly in the urine, about half as unchanged or conjugated drug; clearance falls in kidney impairment.
- Half-life
- About 5–6 hours with normal kidney function.
- Onset and duration
- 1–3 minutes after an IV dose, 10–15 minutes IM and 30–60 minutes by mouth; the effect lasts 1–2 hours.
Indications
- Symptoms of diabetic gastroparesis (short courses). Gastroparesis (delayed gastric emptying) →
- Symptomatic, documented gastro-oesophageal reflux in adults who do not respond to conventional therapy (courses of a few weeks). Gastro-oesophageal reflux disease (GERD) →
- Prevention of nausea and vomiting from chemotherapy and after surgery.
- Helping a feeding tube pass the pylorus and speeding barium transit in radiology.
Adverse effects
Common
- Restlessness, drowsiness and fatigue
- Akathisia (inner restlessness, inability to sit still)
- Diarrhoea
- Raised prolactin: galactorrhoea, menstrual changes, gynaecomastia
Contraindications
- History of tardive dyskinesia or a dystonic reaction to metoclopramide
- Gastrointestinal bleeding, mechanical obstruction or perforation
- Phaeochromocytoma or other catecholamine-releasing paragangliomas (hypertensive crisis)
- Epilepsy (more frequent and severe seizures)
- Hypersensitivity to metoclopramide
Key interactions
- Antipsychotics
- More tardive dyskinesia, other extrapyramidal effects and neuroleptic malignant syndrome; the combination is avoided.
- Strong CYP2D6 inhibitors (fluoxetine, paroxetine, bupropion, quinidine)
- Higher metoclopramide levels and more extrapyramidal effects.
- Levodopa and dopamine agonists
- Opposite effects on dopamine: each weakens the other and parkinsonism can worsen.
- Succinylcholine and mivacurium
- Longer neuromuscular block, because metoclopramide inhibits plasma cholinesterase.
- MAO inhibitors
- Higher risk of hypertension; the combination is avoided.
- Opioids and anticholinergics
- They oppose its effect on gut motility; opioids also add sedation.
- Insulin
- Faster gastric emptying changes when glucose from food arrives; glucose is checked.
What is monitored
- Abnormal movements of the face, tongue or limbs at every visit, and total treatment time
- Mood and suicidal thoughts
- Blood pressure, especially IV and in hypertension
- Blood glucose in people on insulin
- Cyanosis or low oxygen saturation in newborns (methaemoglobinaemia)
Administration and safety
- Undiluted IV doses are injected slowly; a fast injection causes a sudden, intense feeling of anxiety and restlessness
- When diluted, it is infused slowly over the time set in the label
- The solution is light-sensitive and is discarded if discoloured or with particles
- Course length is limited: in diabetic gastroparesis, total use beyond 12 weeks is avoided
Nursing care
- Check for prior abnormal movements, Parkinson disease, seizures and use of antipsychotics before the first dose
- Watch for dystonia (twisted neck, eyes rolling up, jaw spasm) in the first hours, mainly in children and young adults
- Teach the patient and family to report lip smacking, tongue movements or grimacing at once
- Warn about drowsiness and avoiding alcohol or driving if affected
- Ask about low mood and suicidal thoughts during treatment
Pregnancy and breastfeeding
It crosses the placenta; given near delivery it can cause extrapyramidal signs and methaemoglobinaemia in the newborn, who is watched for them.
Test yourself
Think of the answer, then tap the question to see it.
What is metoclopramide's boxed warning, and what limits it in diabetic gastroparesis?
Tardive dyskinesia, which may be irreversible; total treatment beyond 12 weeks is avoided.
Why is metoclopramide contraindicated in suspected bowel obstruction or GI bleeding?
It stimulates upper GI motility, which could worsen an obstruction, a perforation or bleeding.
Why can metoclopramide trigger a hypertensive crisis in an undiagnosed phaeochromocytoma?
It can make the tumour release catecholamines.
A patient taking fluoxetine starts metoclopramide and develops akathisia. What explains it?
Fluoxetine strongly inhibits CYP2D6, so metoclopramide levels rise and extrapyramidal effects become more likely.
Related drugs
Related conditions
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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 - METOCLOPRAMIDE injection, solution (DailyMed (U.S. National Library of Medicine), 2026); DailyMed - METOCLOPRAMIDE tablet (DailyMed (U.S. National Library of Medicine), 2026); RCSB PDB - 6LUQ: Haloperidol bound D2 dopamine receptor structure inspired discovery of subtype selective ligands (RCSB Protein Data Bank, 2026); eEML - Electronic Essential Medicines List (World Health Organization, 2025).
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Representative model, for educational purposes only.