EFFECTS OF THE CALCIUM-ANTAGONIST AE0047 ON THE DEVELOPMENT OF NEUROLOGICAL DEFICIT AND INFARCTION AFTER MIDDLE CEREBRAL-ARTERY OCCLUSION IN STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS

AE0047 [4-(4-benzhydrylpiperazino)phenethyl methyl ihydro-2,6-dimethyl -4-(3-nitrophenyl)-3,5-pyridine dicarboxylate dihydrochloride] is a ne w dihydropyridine calcium antagonist with protective effects against c erebral ischaemia and the occurrence of stroke in several animal model s. We investigated the effects of AE0047 on focal ischaemia induced by middle cerebral artery occlusion in stroke-prone spontaneously hypert ensive rats. AE0047 at a dose causing 20 or 40% systemic hypotension ( 1 or 3 mg kg(-1)) was given orally twice, 15 min and 24 h after occlus ion. The neurological status of animals was investigated 2, 24 and 48 h after occlusion. Infarct area of brain was measured 48 h after occlu sion. Middle cerebral artery occlusion resulted in the progressive det erioration of neurological status and large infarction in middle cereb ral artery territories with 40% mortality. AE0047 dose-dependently att enuated the deterioration of neurological status, and reduced mortalit y to 0 or 10%. AE0047 significantly reduced infarct size and left/righ t hemispheric area ratio, an index of brain swelling. These results su ggest that AE0047 has the ability to ameliorate ischaemic cerebral str oke in hypertensive patients.