Remem 10 Mechanism of Action

Pharmacology: Pharmacodynamics: Mechanism of Action: Memantine hydrochloride is a low to moderate affinity, noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist which binds to NMDA receptor-operated cation channels. Memantine also blocks the 5-hydroxytryptamine-3 receptor (at a potency similar to the NMDA receptor) and nicotinic acetylcholine receptors (at one-sixth to one-tenth the potency). However, memantine has low to negligible affinity for gamma-aminobutyric acid, benzodiazepine, dopamine, adrenergic, histamine, and glycine receptors and for voltage-dependent calcium, sodium, or potassium channels.
Pharmacokinetics: Memantine is well-absorbed after oral administration and has linear pharmacokinetics over the therapeutic dose range. Following oral administration, memantine is highly absorbed with peak concentrations reached in about 3 to 7 hours. The mean volume of distribution of memantine is 9 to 11 L/kg, and the plasma protein binding is low (45%). Memantine undergoes partial hepatic metabolism; about 48% of administered drug is excreted unchanged in urine. The remainder is converted primarily to 3 polar metabolites, which posses minimal NMDA receptor antagonists activity; N-glucuronide conjugate, 6-hydroxy memantine, and 1-nitroso-deaminated memantine. A total of 74% of the administered dose is excreted as the sum of the parent drug and the N-glucuronide conjugate. The hepatic microsomal cytochrome P450 (CYP-450) enzyme system does not play a significant role in the metabolism of memantine. Renal clearance involves active tubular secretion moderated by pH-dependent tubular reabsorption. Memantine has a terminal elimination half-life of about 60 to 80 hours.