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
H. Shinyama et al., 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, Journal of Pharmacy and Pharmacology, 49(9), 1997, pp. 919-924
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.