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钙通道阻滞剂盐酸贝尼地平对实验性脑缺血/缺氧的作用

[Effect of efonidipine hydrochloride, a calcium channel blocker, on the experimental cerebral ischemia/anoxia].

作者信息

Matsumura T, Furuichi H, Izumi J, Suda H, Ito S, Takei M, Nishi N, Mori T, Tanaka Y, Kurimoto T

机构信息

Central Research Laboratories, Zeria Pharmaceutical Co., Ltd., Saitama, Japan.

出版信息

Nihon Yakurigaku Zasshi. 1995 Jun;105(6):437-46. doi: 10.1254/fpj.105.437.

Abstract

The anti-ischemic and anti-anoxic effects of efonidipine, a dihydropyridine calcium antagonist, were studied in several models for cerebral ischemia and anoxia in mice and rats, and the effects were compared with those of nicardipine and flunarizine. Both efonidipine and flunarizine showed protective effects in the models of KCN-induced anoxia and complete ischemia induced by decapitation in mice 6 hr after the treatment, while nicardipine did not show such a long-lasting effect. Efonidipine (1 mg/kg, i.p.), but not nicardipine and flunarizine, prolonged the tolerance times in the asphyxic anoxia model. In mice, efonidipine (4 mg/kg, i.p.) significantly reduced the cumulative mortality rate after bilateral carotid artery ligation. The survival rates at 20 hr after bilateral carotid artery ligation were 33% in the group treated with efonidipine, significantly higher than that in the control group, 0%. On the other hand, the treatment with nicardipine or flunarizine did not increase the rates at 20 hr after the ligation. Moreover, efonidipine attenuated the disturbance of cerebral energy metabolism induced by decapitation in rats. These effects of efonidipine observed in this study were on the whole superior to those of the reference drugs, strongly suggesting the improving effect of efonidipine on cerebral ischemia and anoxia.

摘要

对二氢吡啶类钙拮抗剂依福地平的抗缺血和抗缺氧作用进行了研究,采用了小鼠和大鼠的几种脑缺血缺氧模型,并将其作用与尼卡地平和氟桂利嗪进行了比较。依福地平和氟桂利嗪在处理6小时后的小鼠氰化钾诱导缺氧和断头诱导的完全缺血模型中均显示出保护作用,而尼卡地平未显示出如此持久的作用。依福地平(1mg/kg,腹腔注射)而非尼卡地平和氟桂利嗪延长了窒息性缺氧模型中的耐受时间。在小鼠中,依福地平(4mg/kg,腹腔注射)显著降低了双侧颈动脉结扎后的累积死亡率。双侧颈动脉结扎20小时后,依福地平治疗组的存活率为33%,显著高于对照组的0%。另一方面,尼卡地平或氟桂利嗪治疗并未增加结扎后20小时的存活率。此外,依福地平减轻了大鼠断头诱导的脑能量代谢紊乱。本研究中观察到的依福地平的这些作用总体上优于参比药物,强烈提示依福地平对脑缺血和缺氧具有改善作用。

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引用本文的文献

1
A selective T-type Ca2+ channel blocker R(-) efonidipine.一种选择性T型钙离子通道阻滞剂R(-)依福地平。
Naunyn Schmiedebergs Arch Pharmacol. 2008 Jun;377(4-6):411-21. doi: 10.1007/s00210-007-0239-6. Epub 2008 Feb 16.

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