Molax/Molax-M Mechanism of Action

Pharmacology: Pharmacodynamics: Domperidone is a dopamine antagonists (both D₁ receptors - facilitates gastrointestinal smooth muscle activity; and D₂ receptors - inhibit the release of neural acetylcholine), structurally related to the benzimidazole. It has peripheral anticholinergic properties relating to gastroprokinetics properties; it facilitates gastric emptying and decreases small bowel transit time by increasing esophageal and gastric peristalsis and by lowering esophageal sphincter pressure. It also has antiemetic properties relating to dopaminergic blocking activity at both the chemoreceptor trigger zone (in the brainstem) and at the gastric level. It also elevates serum prolactin concentrations. It has no effect on the receptors of the brain (not readily crosses the blood-brain barriers), so that psychotropic or neurologic effects are practically absent.
Pharmacokinetics: Domperidone can be absorbed rapidly after oral doses. The absorption is decreased by the prior administration of cimetidine or sodium bicarbonate. The systemic bioavailability of Domperidone is only about 15% in fasting subjects given an oral dose; this is increased when domperidone is given 90 minutes after food. The low availability is thought to be due to first-pass hepatic and intestinal metabolism. It is more than 90% bound to plasma proteins and has a terminal elimination half-life of about 7.5 hours (prolonged to 21 hours in patients with severe renal dysfunction; serum creatinine greater than 530 mmol/L). It does not accumulate upon repeated administration. It undergoes rapid and extensive hepatic metabolism. The main metabolic pathways are N-dealkylation by cytochrome P450 isoenzyme CYP3A4, and aromatic alkylation by CYP3A4, CYP1A2, and CYP2E1; yielding 2 inactive metabolites. About 30% of an oral dose is excreted in urine within 4 days, almost entirely as metabolites; the remainder of a dose is excreted in faeces over several days, about 10% as unchanged drug. It does not readily cross the blood-brain barrier. Small amounts of the drug are distributed into breast milk; concentrations are 10-50% of those in maternal serum.