Neuroprotective effect of D-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid in the gerbil model of transient global cerebral ischemia

被引:0
|
作者
Okada, M
Ueda, H
Kometani, M
Nakao, K
Kohjimoto, Y
Takahashi, I
Tanaka, I
机构
[1] CIBA GEIGY LTD, DIV PHARMACEUT, DRUG DISCOVERY RES UNIT, RES & DEV SUBDIV, TAKARAZUKA, HYOGO, JAPAN
[2] PANAFARM LABS, LAB PHARMACOKINET & PHARMACOL, UDO, KUMAMOTO, JAPAN
来源
ARZNEIMITTELFORSCHUNG-DRUG RESEARCH | 1997年 / 47卷 / 06期
关键词
D-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid; CAS110347-85-8; CAS137424-81-8; cerebral ischemia; experimental; CGP40116; pharmacology; CGS19755; N-methyl-D-aspartate antagonists; (+/-)-cis-4-phosphonomethylpiperadine-2-carboxylic acid;
D O I
暂无
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Effect of the new competitive N-methyl-D-aspartate (NMDA) antagonist D-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid (GAS 137424-81-8, CGP 40116) was examined in a mongolian gerbil model of global cerebral ischemia. Effect of CGP 40116 was compared to that of another competitive NMDA antagonist, (+/-)-cis-4-phosphonomethyl-piperadine-2-carboxylic acid (GAS 110347-85-8, CGS 19755) under the same conditions. Drugs were administered intraperitoneally 30 min before bilateral carotid artery occlusion. At 4 days after the ischemia, locomotor activity was significantly higher in ischemic control mongolian gerbils in comparison with sham-operated mongolian gerbils. CGP 40116 at the dose of 10 mg/kg and CGS 19755 at the doses of 10 and 30 mg/kg significantly suppressed the increase of the motility. Seven days after ischemia, ischemic control group was still hyperactive compared to sham-operated group. CGP 40116 at the dose of 10 mg/kg and CGS 19755 at the dose of 30 mg/kg significantly reversed it. The number of survived neurons of ischemic control group was significantly less than that of sham-operated group at 7 days after ischemia. CGP 40116 at the dose of 10 mg/kg and CGS 19755 at the dose of 30 mg/kg significantly increased the number of survived neurons. It is concluded that CGP 40116 is more potent for amelioration of global cerebral ischemic damage than CGS 19755.
引用
收藏
页码:700 / 702
页数:3
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