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.
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 effect itself may also contribute to the anti-emetic effect.
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 In nausea and vomiting associated with cancer chemotherapy, it has been superseded by the more effective 5-HT3 antagonists (e.g. ondansetron).
Common adverse drug reactions (ADRs) associated with metoclopramide therapy include: restlessness, drowsiness, dizziness, lassitude, and/or dystonic reactions. Infrequent ADRs include: headache, extrapyramidal effects (EPSE) such as oculogyric crisis, 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 is 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 prolonged use. Tardive dyskinesias may be persistent and irreversible in some patients.