Metoclopramide: pharmacology and clinical application.
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Metoclopramide antagonizes the effect of dopamine in the central nervous system and other organ systems. Metoclopramide's effect on the medullary chemoreceptor trigger zone makes it useful as a routine anti-emetic and in preventing vomiting induced by antineoplastic drugs, particularly cisplatin. Metoclopramide's gastrointestinal smooth muscle stimulatory effects are related to its ability to antagonize the inhibitory neurotransmitter, dopamine; to augment acetylcholine release and sensitize the muscarinic receptors of the gastrointestinal smooth muscle; and to coordinate gastric-pyloric-small intestinal motor function. The indications for which metoclopramide is approved in the United States are reviewed. Adverse effects, which may occur in up to 20% of patients, include drowsiness, lassitude, and akathisia; all are usually mild, transient, and reversible. Tremor, dystonic reactions, and extrapyramidal effects are infrequent; breast enlargement, galactorrhea, and menstrual irregularities are related to prolactin release.