NICARDIPINE AND TREATMENT OF CEREBROVASCULAR DISEASES WITH PARTICULARREFERENCE TO HYPERTENSION-RELATED DISORDERS

Nicardipine is a second generation dihydropyridine-type Ca2+ antagonis t with high vascular selectivity and strong cerebral and coronary vaso dilatory activity. The compound is used in the treatment of hypertensi on, primarily in the elderly. In this review the main evidence of the cerebrovascular activity of nicardipine in preclinical studies using i n vitro and in vivo models is detailed. A particular physico-chemical property of nicardipine is the almost complete protonation in acid env ironment. This allows its accumulation in ischemic brain regions and m akes it a candidate for the treatment of cerebrovascular disorders cha racterised by impaired brain perfusion. The main clinical data on the use of nicardipine in cerebral ischemia and related disorders, subarac hnoid haemorrhage and stroke, are also reviewed. These studies include d 5940 patients affected by chronic cerebrovascular insufficiency (cer ebral ischemia, cerebral atherosclerosis mainly associated with hypert ension, transient ischemic: attacks, sequelae of cerebral infarction, thrombosis or embolia, hypertensive encephalopathy), 1540 patients aff ected by sequelae of subarachnoid haemorrhage and 206 patients affecte d by stroke. Both preclinical studies and clinical trials have shown t hat nicardipine is a safe Ca2+ antagonist with powerful cerebrovascula r activity. This suggests its possible use In cerebrovascular disorder s in which blockade of Ca2+ channels of the L-type and/or selective ce rebral vasodilatation is desirable. Further studies are necessary to e stablish if modulation of neuronal Ca2+ channels of the L-type by nica rdipine may have a neuroprotective effect independent by the cerebrova scular activity of the compound.