Metoclopramide

A potent dopamine D2 receptor antagonist with Ki of 28 nM; also is a mixed 5-HT3 receptor antagonist/5-HT4 receptor agonist; commonly used to treat nausea and vomiting caused by chemotherapy.Chemotherapeutic Agents Phase 2 Discontinued(In Vitro):Metoclopramide (0.01-10 μM) stimulates aldosterone release in isolated perfused rat zona glomerulosa cells.Metoclopramide results in prokinesis by four mechanisms: inhibition of presynaptic D2 receptors and stimulation of presynaptic excitatory 5-HT4 receptors, thereby allowing acetylcholine (ACh) release from intrinsic cholinergic motor neurons; inhibition of D2 postsynaptic receptors; and antagonism of the presynaptic inhibition of muscarinic receptors, leading to further augmentation of ACh release.(In Vivo):Metoclopramide (6.7 μg/g; s.c. daily for 50 days) significantly increases the number and the volume of lactotroph cells of the pituitary gland during all phases of the estrous cycle.Metoclopramide (5-40 mg/kg; i.p.) induces catalepsy and antagonizes Apomorphine induced cage climbing behaviour in mice.Metoclopramide (1.25-2.5 mg/kg; i.p.) induces stereotyped cage climbing behaviour in mice.