YM90K, an AMPA receptor antagonist, protects against ischemic damage caused by permanent and transient middle cerebral artery occlusion in rats

被引:18
作者
Kawasaki-Yatsugi, S [1 ]
Ichiki, C [1 ]
Yatsugi, S [1 ]
Shimizu-Sasamata, M [1 ]
Yamaguchi, T [1 ]
机构
[1] Yamanouchi Pharmaceut Co Ltd, Inst Drug Discovery Res, Pharmacol Lab, Tsukuba, Ibaraki 3058585, Japan
关键词
YM90K; alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor; focal cerebral ischemia;
D O I
10.1007/PL00005297
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The neuroprotective effect of YM90K, a potent AMPA receptor antagonist, was examined in rats with permanent and transient occlusion of middle cerebral artery (MCA) using intraluminal suture occlusion method. In rats with permanent MCA occlusions, two types of occluders were used to compare the efficacy of YM90K. When a 4-0 (diameter: 0.19 mm) suture was used, YM90K (20 mg kg(-1) h(-1) i.v. infusion for 4 h) significantly reduced infarct volume (P<0.05) and neurologic deficits (P<0.05) 24 h after MCA occlusion. Infarct volume was also reduced by YM90K at the same dose (P<0.01) when severe ischemia was induced by a 3-0 (diameter: 0.23 mm) suture. In rats with transient (3 h) MCA occlusions, a IO-mg kg(-1) h(-1) dose of YM90K that did not show significant protection in rats with permanent MCA occlusion offered neuroprotective effects. These data demonstrate that YM90K provides cerebral neuroprotection against a wide range of ischemic insults.
引用
收藏
页码:586 / 591
页数:6
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