Metoclopramide is both a dopaminergic receptor antagonist and a selective peripheral cholinergic agonist. The antiemetic effect is attributed to the central and peripheral dopamine receptor inhibition.It reduces gastric fluid volume by stimulating upper gastrointestinal motility, enhancing gastric emptying, and increasing the lower esophageal sphincter tone.It hastens motility in the upper gastrointestinal tract by sensitizing tissues to the action of acetylcholine, which is independent from intact vagal innervation and does not stimulate biliary, gastric, or pancreatic secretions.It hastens gastric emptying and intestinal transit by increasing tone and amplitude of gastric contractions, relaxing the pyloric sphincter and duodenal bulb, and enhancing peristalsis of the duodenum and jejunum.It is not known to decrease the gastric fluid pH. Its gastrokinetic effect is opposed by atropine and opioids.
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