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Metoclopramide (INN) (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), Maxeran and Primperan (Sanofi Aventis).

Reglan Drug
Mode of action
Metoclopramide was first described by Louis Justin-Besançon and C. Laville in 1964 (Justin-Besançon & Laville, 1964). It selectively binds to dopamine D2 receptors where it is a receptor antagonist, but in higher doses there is also some antagonist activity at 5-HT3 receptors.

Specifically, metoclopramide is able to enter the central nervous system and antagonise the D2 receptors in the chemoreceptor trigger zone (CTZ) in the brainstem, thus blocking nausea and vomiting caused by most sources.

Clinical use

Antiemetic use
Metoclopramide is commonly used to treat nausea and vomiting (emesis) associated with conditions including: emetogenic drugs, uraemia, radiation sickness, malignancy, labour, and infection (Valeant Pharmaceuticals, 2000; Rossi, 2006). It is also used by itself or in combination with paracetamol for the relief of migraine.

It is considered ineffective in post-operative nausea and vomiting (PONV) at standard doses (Rossi, 2006), and ineffective for motion sickness (Valeant Pharmaceuticals, 2000). In nausea and vomiting associated with cancer chemotherapy, it has been superseded by the more effective 5-HT3 antagonists (e.g. ondansetron).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.

Adverse effects
Common adverse drug reactions (ADRs) associated with metoclopramide therapy include: restlessness, drowsiness, dizziness, and/or headache. Infrequent ADRs include: extrapyramidal effects (EPSE), 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 (Rossi, 2006).

The risk of EPSEs are increased in young adults (<20 years) and children (Rossi, 2006). Such dystonic reactions are usually treated with benztropine. 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 (Valeant Pharmaceuticals, 2000).

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