Shinyama H, Kawamura T, Iwamoto M, Egi Y, Tanaka H, Kawabata Y, Nakamura N, Kagitani Y
Pharmacology Laboratories, Green Cross Corporation, Osaka, Japan.
J Pharm Pharmacol. 1997 Sep;49(9):919-24. doi: 10.1111/j.2042-7158.1997.tb06136.x.
AE0047 [4-(4-benzhydrylpiperazino)phenethyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine dicarboxylate dihydrochloride] is a new dihydropyridine calcium antagonist with protective effects against cerebral ischaemia and the occurrence of stroke in several animal models. We investigated the effects of AE0047 on focal ischaemia induced by middle cerebral artery occlusion in stroke-prone spontaneously hypertensive 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 occlusion. The neurological status of animals was investigated 2, 24 and 48 h after occlusion. Infarct area of brain was measured 48 h after occlusion. Middle cerebral artery occlusion resulted in the progressive deterioration of neurological status and large infarction in middle cerebral artery territories with 40% mortality. AE0047 dose-dependently attenuated the deterioration of neurological status, and reduced mortality to 0 or 10%. AE0047 significantly reduced infarct size and left/right hemispheric area ratio, an index of brain swelling. These results suggest that AE0047 has the ability to ameliorate ischaemic cerebral stroke in hypertensive patients.
AE0047[4-(4-二苯甲基哌嗪基)苯乙基甲基1,4-二氢-2,6-二甲基-4-(3-硝基苯基)-3,5-吡啶二甲酸二盐酸盐]是一种新型二氢吡啶类钙拮抗剂，在多种动物模型中对脑缺血和中风的发生具有保护作用。我们研究了AE0047对易中风自发性高血压大鼠大脑中动脉闭塞所致局灶性缺血的影响。在闭塞后15分钟和24小时，口服给予AE0047，剂量为引起20%或40%全身性低血压的剂量(1或3毫克/千克)，给药两次。在闭塞后2、24和48小时对动物的神经状态进行研究。在闭塞后48小时测量脑梗死面积。大脑中动脉闭塞导致神经状态逐渐恶化，大脑中动脉区域出现大面积梗死，死亡率为40%。AE0047剂量依赖性地减轻神经状态的恶化，并将死亡率降低至0或10%。AE0047显著减小梗死体积，并降低左右半球面积比，这是脑肿胀的一个指标。这些结果表明，AE0047有能力改善高血压患者的缺血性脑中风。
