CGS-19755, A COMPETITIVE NMDA RECEPTOR ANTAGONIST, REDUCES CALCIUM-CALMODULIN BINDING AND IMPROVES OUTCOME AFTER GLOBAL CEREBRAL-ISCHEMIA

被引：106

作者：

GROTTA, JC ^{[1
]}

PICONE, CM ^{[1
]}

OSTROW, PT ^{[1
]}

STRONG, RA ^{[1
]}

EARLS, RM ^{[1
]}

YAO, LP ^{[1
]}

RHOADES, HM ^{[1
]}

DEDMAN, JR ^{[1
]}

机构：

[1] UNIV TEXAS,SCH MED,DEPT PHYSIOL,HOUSTON,TX 77030

来源：

ANNALS OF NEUROLOGY | 1990年 / 27卷 / 06期

关键词：

D O I：

10.1002/ana.410270605

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

We evaluated several doses of cis‐4‐(phosphonomethyl)‐2‐piperidine‐carboxylic acid (CGS‐19755), a potent competitive N‐methyl‐D‐aspartate (NMDA) receptor antagonist, systemically administered either before or after 20 to 30 minutes of global ischemia in rats. We measured outcome by mortality, histological damage by light microscopy, and learning ability on an eight‐arm maze, and determined the drug's mechanism of action by an immunohistochemical assay of calcium‐calmodulin binding. High‐dose treatment begun prior to ischemia resulted in reduced cellular damage in severely ischemic hippocampal tissue, but also caused high mortality due to respiratory depression. Treatment begun 30 minutes after ischemia resulted in little histological protection but significantly improved learning ability when tested 1 month after ischemia, and did not increase mortality. Furthermore, CGS‐19755, 10 mg/kg intraperitoneally, begun either before or after ischemia substantially reduced calcium influx into ischemic neurons as evidenced by reduced calcium‐calmodulin binding. We conclude that CGS‐19755 prevents calcium entry into ischemic neurons and may be effective therapy for very acute cerebral ischemia. Copyright © 1990 American Neurological Association

引用

页码：612 / 619

页数：8

共 25 条

[1] THE N-METHYL-D-ASPARTATE ANTAGONISTS CGS-19755 AND CPP REDUCE ISCHEMIC BRAIN-DAMAGE IN GERBILS [J].