Cilnidipine (FRC-8653)(FRC8653) is a dual L- and N-type calcium channel blocker and displays antihypertensive, sympatholytic and neuroprotective activity.

Cilnidipine inhibits the rise in blood urea nitrogen and the decline in creatinine clearance, as well as the progression of glomerulosclerosis. It prevents the increased content of renal angiotensin II, the expression of NADPH oxidase, and the augmented membrane translocation of dihydroethidium in SHR/ND rats. Administering 30 mg/kg of Cilnidipine daily to Dahl salt-sensitive rats effectively treated the elevation of systolic blood pressure. Compared to control-treated Dahl S rats, Cilnidipine reduced plasma norepinephrine levels and plasma renin activity. In spinal cord destruction rats, it suppressed the pressor responses induced by sympathetic nerve stimulation and angiotensin II. In anesthetized rats, Cilnidipine, or omega-conotoxin MVIIA, lowered mean arterial blood pressure with a slight increase in heart rate. At antihypertensive doses in rats, Cilnidipine affected sympathetic nerve N-type calcium channels (Ca(2+)), besides vascular L-type channels. Following NMDA receptor activation, Cilnidipine reduced Ca(2+) influx through N-type channels, and in rats in vivo, it protected neurons from ischemic reperfusion injury in the retina. Compared to amlodipine-treated spontaneously hypertensive rats/ND mcr-cp (SHR/ND), Cilnidipine significantly prevented the increase in fibrillary protein staining and restored the expression of podocin and nephrin in the glomeruli.

Cilnidipine at 10 mM can inhibit the increase in the ratio induced by 40 mM potassium chloride, and is also effective in inhibition when treated with omega-conotoxin GVIA.