Kawaguchi K, Graham S H
Department of Neurology, University of Pittsburgh, PA 15213, USA.
Brain Res. 1997 Feb 21;749(1):131-4. doi: 10.1016/s0006-8993(96)01311-x.
619C89 is a use-dependent Na+ channel antagonist that decreases the release of glutamate during ischemia. The efficacy of this drug in reducing infarction volume 72 h after occlusion of the middle cerebral artery (MCA) for 2 h in rats (n = 93) was determined by analysis of TTC-stained coronal section of the brain. Doses of 10, 20, 30 and 50 mg/kg of study drug given i.v. prior to MCA occlusion significantly (P < 0.05-0.01) reduced infarction volume in cortex compared to vehicle controls. Only the 50 mg/kg dose reduced infarction volume in the striatum (P < 0.05). Administration of 50 mg/kg of 619C89 30 and 60 min after the onset of ischemia reduced cortical infarction volume (P < 0.05), but there was no effect when the drug was given 5 min after reperfusion. No post-treatment regimen reduced striatal infarction volume. These results confirm the neuroprotective effects of 619C89 in temporary focal ischemia.
619C89是一种依赖于使用的钠离子通道拮抗剂，可在缺血期间减少谷氨酸的释放。通过对大鼠（n = 93）大脑中动脉（MCA）闭塞2小时后72小时梗死体积的分析，确定了该药物在减少梗死体积方面的疗效。在MCA闭塞前静脉注射10、20、30和50mg/kg的研究药物剂量，与载体对照组相比，皮质梗死体积显著降低（P < 0.05 - 0.01）。只有50mg/kg剂量降低了纹状体梗死体积（P < 0.05）。在缺血发作后30分钟和60分钟给予50mg/kg的619C89可减少皮质梗死体积（P < 0.05），但在再灌注后5分钟给予药物则没有效果。没有后处理方案能减少纹状体梗死体积。这些结果证实了619C89在短暂性局灶性缺血中的神经保护作用。
