Nimodipine is used to treat symptoms resulting from a ruptured blood vessel in the brain (subarachnoid hemorrhage). It works by increasing the blood flow to injured brain tissue. This medicine is available only with your doctor's prescription. Chemically, nimodipine is a lipophilic dihydropyridine L-type calcium channel blocker that preferentially targets cerebral vasculature and has the ability to cross the blood brain barrier, providing cerebrovascular selective vasodilation and neuronal protection in ischemic penumbra. It is formulated primarily for oral administration as immediate release capsules and oral liquid preparations; absorption is rapid with peak plasma concentrations typically within about 1 hour and systemic exposure is substantially affected by first pass hepatic metabolism. Therapeutic monitoring and dose adjustments are considered in patients with severe hepatic impairment and when coadministered with strong CYP3A4 inhibitors or inducers because nimodipine is extensively metabolized by CYP3A enzymes. Standard clinical dosing after aneurysmal subarachnoid hemorrhage is time limited and administered under hospital supervision to reduce the risk of cerebral vasospasm.
Parent: Nimodipine
Manufacturing and quality control focus on limiting related substances and degradation products that can arise from hydrolysis, oxidation, dealkylation and dehydrogenation of the dihydropyridine ring and ester moieties; common related compounds include de-esterified acid derivatives, N-dealkylated species, dehydro-nimodipine and minor oxidized or ring opened products. Typical pharmaceutical control criteria used by manufacturers and pharmacopoeias include assay acceptance around 98.0 to 102.0 percent of label claim, individual specified related substances commonly limited to 0.1 to 0.2 percent by HPLC, unspecified individual impurities often limited to 0.1 percent, and total impurities typically limited to 0.5 percent or less. Residual solvents and elemental impurities are controlled according to ICH guidelines with limits applied for common solvents used in synthesis and purification. Stability testing includes assessment of humidity, heat, light and pH dependent degradation pathways to define storage conditions and shelf life.
Nimodipine is used to reduce the incidence and severity of ischemic neurological deficits associated with cerebral vasospasm following subarachnoid hemorrhage from a ruptured cerebral aneurysm.
Nimodipine can lower systemic blood pressure because it relaxes vascular smooth muscle, but at therapeutic doses used for subarachnoid hemorrhage it is dosed to maximize cerebral blood flow while monitoring systemic blood pressure to avoid hypotension.
Nimodipine inhibits L-type voltage dependent calcium channels in vascular smooth muscle and neurons, reducing calcium influx, causing vasodilation of cerebral arteries and decreasing calcium mediated neuronal injury in ischemic tissue.
Yes, nimodipine is a vasodilator with relative selectivity for cerebral vasculature, which contributes to its clinical benefit in preventing or treating cerebral vasospasm after subarachnoid hemorrhage.
