Cilnidipine

A dual L- and N-type calcium channel blocker that displays antihypertensive, sympatholytic and neuroprotective activity. Hypertension Approved(In Vitro):Cilnidipine inhibits the L-type current with an IC50 of 100 nM in neurons pretreated with omegaCgTx plus omegaAgTx.The IC50 for Cilnidipine in respect of the N-type current is 200 nM.Cilnidipine dose- and time-dependently inhibits Ba2+ currents in A7r5 cells with the IC50 at 10 nM after 10 min.Cilnidipine dose-dependently inhibits depolarization- and Ca2+-induced contractions of rat aortic rings, with an IC50 of 10 nM at 10 min.The viability of nPC12 cells show no significant change up to 150 μM Cilnidipine, but it decreases slightly in the cells treated with greater than 200 μM Cilnidipine.Cilnidipine (100 μM, 2 hours) treatment increases the expression of p85aPI3K p-Akt, p-GSK-3β, and heat shock transcription factor (HSTF-1), and decreases levels of cytosolic cytochrome c, activated caspase 3, and cleaved PARP.\n(In Vivo):Cilnidipine has potent inhibitory actions on N-type as well as L-type voltage-dependent Ca2+-channel in rat dorsal root ganglion neurons.Administration of Cilnidipine (10 mg/kg) and Nimodipine (10 mg/kg) significantly attenuates the immobilized stress-induced behavioral changes and restored memory deficits along with normalization of the corticosterone levels.Cilnidipine and Nimodipine produce comparable beneficial effects in restoring immobilization stress subjected mice.Oral administration of Cilnidipine (3 mg/kg) markedly lowers both systolic and diastolic blood pressure 1 hr after administration in 2K1C renal hypertensive dogs.