Metoclopramide (injection)

Metoclopramide (injection)

Clinical data
Pregnancy category	A (Au), B (U.S.)
Routes of administration	Oral, IV, IM
ATC code	A03FA01 (WHO)
Legal status
Legal status	S3/S4 (Au), POM (UK), ℞-only (U.S.)
Pharmacokinetic data
Bioavailability	80±15% (oral)
Metabolism	Hepatic
Elimination half-life	5–6 hours
Excretion	70–85% renal, 2% faecal
Identifiers
IUPAC name 4-amino-5-chloro-N-(2-(diethylamino)ethyl)- 2-methoxybenzamide
CAS Number	364-62-5
PubChem CID	4168
DrugBank	APRD00665
E number	{{#property:P628}}
ECHA InfoCard	{{#property:P2566}}
Chemical and physical data
Formula	C14H22ClN3O2
Molar mass	299.80 g/mol

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Metoclopramide (INN) (IPA: Template:IPA) is a potent dopamine receptor antagonist used for its antiemetic and prokinetic properties. Thus it is primarily used to treat nausea and vomiting, and to facilitate gastric emptying in patients with gastric stasis.

It is available under various trade names including: Maxolon (Shire/Valeant), Reglan (Wyeth), Degan (Lek), Maxeran (Sanofi Aventis), Primperan (Sanofi Aventis), and Pylomid (Bosnalijek). It was protected under U.S. patent 3177252 until 6 April 1982.

Mode of action

Metoclopramide was first described by Dr. Louis Justin-Besançon and C. Laville in 1964. It appears to bind to dopamine D2 receptors where it is a receptor antagonist, and is also a mixed 5-HT₃ receptor antagonist/5-HT₄ receptor agonist.

The anti-emetic action of metoclopramide is due to its antagonist activity at D2 receptors in the chemoreceptor trigger zone (CTZ) in the central nervous system (CNS)—this action prevents nausea and vomiting triggered by most stimuli. At higher doses, 5-HT₃ antagonist activity may also contribute to the anti-emetic effect.

The prokinetic activity of metoclopramide is mediated by muscarinic activity, D2 receptor antagonist activity and 5-HT₄ receptor agonist activity. The prokinetic itself may also contribute to the anti-emetic effect.

Clinical use

Antiemetic use

Metoclopramide is commonly used to treat nausea and vomiting (emesis) associated with conditions including: emetogenic drugs, uraemia, radiation sickness, malignancy, labor, and infection. It is also used by itself or in combination with paracetamol (acetaminophen) for the relief of migraine.

It is considered ineffective in postoperative nausea and vomiting (PONV) at standard doses, and ineffective for motion sickness. In nausea and vomiting associated with cancer chemotherapy, it has been superseded by the more effective 5-HT₃ antagonists (e.g. ondansetron).

Prokinetic use

Metoclopramide increases peristalsis of the jejunum and duodenum, increases tone and amplitude of gastric contractions, and relaxes the pyloric sphincter and duodenal bulb. These prokinetic effects make metoclopramide useful in the treamtent of gastric stasis (e.g. after gastric surgery or diabetic gastroparesis), as an aid in gastrointestinal radiology by increasing transit in barium studies, and as an aid in difficult small intestinal intubation. It is also used in gastroesophageal reflux disease (GERD/GORD).

Other indications

By inhibiting the action of prolactin inhibiting hormone (i.e. dopamine), metoclopramide has sometimes been used to stimulate lactation.

Contraindications/precautions

Metoclopramide is contraindicated in phaeochromocytoma. It should be used with caution in Parkinson's disease since, as a dopamine antagonist, it may worsen symptoms. Long-term use should be avoided in patients with clinical depression as it may worsen mental state. Also contraindicated with a suspected bowel obstruction.

Adverse effects

Plastic ampoule of metoclopramide

Common adverse drug reactions (ADRs) associated with metoclopramide therapy include: restlessness, drowsiness, dizziness, and/or headache. Infrequent ADRs include: extrapyramidal effects (EPSE) such as oculogyric crisis (and other acute dystonic reactions), hypertension, hypotension, hyperprolactinaemia leading to galactorrhoea, diarrhoea, constipation, and/or depression. Rare but serious ADRs associated with metoclopramide therapy include: agranulocytosis, supraventricular tachycardia, hyperaldosteronism, neuroleptic malignant syndrome and/or tardive dyskinesia.

The risk of EPSEs are increased in young adults (<20 years) and children. Such dystonic reactions are usually treated with benztropine or procyclidine. The risk of tardive dyskinesia and EPSE is increased with high dose therapy and with prolonged use. Tardive dyskinesias may be persistent and irreversible in some patients.

Further reading

• Brenner GM. Pharmacology. London: W B Saunders; 2000 ISBN 0-7216-7757-6
• Canadian Pharmacists Association. Compendium of Pharmaceuticals and Specialties. 25th ed. Toronto: Webcom; 2000. ISBN 0-919115-76-4
• Practical Gastroenterology May 2004 Recognition of Movement Disorders and Extrapyramidal side effects - would you recognize them if you see them?. Available on practicalgastro.com