首页 | 本学科首页   官方微博 | 高级检索  
     


A multifunctional cytoprotective agent that reduces neurodegeneration after ischemia
Authors:Jiang Zhi-Gang  Lu X-C May  Nelson Valery  Yang Xiaofang  Pan Weiying  Chen Ren-wu  Lebowitz Michael S  Almassian Bijan  Tortella Frank C  Brady Roscoe O  Ghanbari Hossein A
Affiliation:Panacea Pharmaceuticals, Inc., Gaithersburg, MD 20877, USA. zgjiang@panaceapharma.com
Abstract:Cellular and molecular pathways underlying ischemic neurotoxicity are multifaceted and complex. Although many potentially neuroprotective agents have been investigated, the simplicity of their protective mechanisms has often resulted in insufficient clinical utility. We describe a previously uncharacterized class of potent neuroprotective compounds, represented by PAN-811, that effectively block both ischemic and hypoxic neurotoxicity. PAN-811 disrupts neurotoxic pathways by at least two modes of action. It causes a reduction of intracellular-free calcium as well as free radical scavenging resulting in a significant decrease in necrotic and apoptotic cell death. In a rat model of ischemic stroke, administration of PAN-811 i.c.v. 1 h after middle cerebral artery occlusion resulted in a 59% reduction in the volume of infarction. Human trials of PAN-811 for an unrelated indication have established a favorable safety and pharmacodynamic profile within the dose range required for neuroprotection warranting its clinical trial as a neuroprotective drug.
Keywords:
本文献已被 PubMed 等数据库收录!
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号