Nimotop Mechanism of Action

Pharmacology: Pharmacodynamics: Nimodipine has a predilective cerebral anti-vasoconstrictive and anti-ischaemic activity. Vasoconstrictions provoked in vitro by various vasoactive substances (e.g. serotonin, prostaglandins, and histamine) or by blood and blood degradation products can be prevented or eliminated by nimodipine. Nimodipine also has neuropharmacological and psychopharmacological properties.
Investigations in patients with acute cerebral blood flow disturbances have shown that nimodipine dilates the cerebral blood vessels and promotes cerebral blood flow. The increase in perfusion is as a rule greater in previously damaged or underperfused brain region than in healthy regions.
The ischemic neurological damage in patients with subarachnoid hemorrhage and the mortality rate are significantly reduced by nimodipine.
Pharmacokinetics: Absorption: The orally administered active substance nimodipine is practically completely absorbed. The peak plasma concentration and the area under the curve increase proportionally to the dose up to the highest dose under test (90 mg).
The distribution volume (Vss, 2-compartment model) for i.v. administration is calculated to be 0.9 - 1.6 l/kg body weight. The total (systemic) clearance is 0.6 - 1.9 l/h/kg.
Protein binding and distribution: Nimodipine is 97 - 99 % bound to plasma proteins.
Metabolism, elimination and excretion: Nimodipine is eliminated metabolically via the cytochrome P450 3A4 system.
Bioavailability: Attributed to the extensive first-pass metabolism (about 85 - 95 %) the absolute bioavailability is 5 - 15 %.
Toxicology: Preclinical safety data: Preclinical data reveal no special hazard for humans based on conventional studies of single and repeated dose toxicity, genotoxicity, carcinogenicity and male and female fertility. In pregnant rats, doses of 30 mg/kg/day and higher inhibited foetal growth and resulted in reduced foetal weights. At 100 mg/kg/day embryolethality occurred. No evidence of teratogenicity was observed. In rabbits, no embryotoxicity and teratogenicity occurred at doses up to 10 mg/kg/day. In one peri-postnatal study in rats, mortality and delayed physical development were observed at doses of 10 mg/kg/day and higher. The findings were not confirmed in subsequent studies.