Mechanism 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 antiemetic 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 antiemetic effect.
The gastroprokinetic activity of metoclopramide is mediated by muscarinic activity, D2 receptor antagonist activity and 5-HT4 receptor agonist activity. The gastroprokinetic effect itself may also contribute to the antiemetic effect. Metoclopramide also increases the tone of the lower esophageal sphincter.
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