NEUROPROTECTIVE AND ANTIOXIDANT ACTIVITIES OF HU-211, A NOVEL NMDA RECEPTOR ANTAGONIST

被引:79
作者
ESHHAR, N [1 ]
STRIEM, S [1 ]
KOHEN, R [1 ]
TIROSH, O [1 ]
BIEGON, A [1 ]
机构
[1] HEBREW UNIV JERUSALEM,SCH PHARM,DEPT PHARM,IL-91120 JERUSALEM,ISRAEL
关键词
TOXICITY; ANTIOXIDANT; FREE RADICAL; NMDA RECEPTOR; CORTICAL CULTURE;
D O I
10.1016/0014-2999(95)00271-L
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
This study examines the ability of (+)-(3S,4S)-7-hydroxy-Delta(6)-tetrahydrocannabinol-1,1-dimethylheptyl (HU-211), a non-competitive NMDA receptor antagonist to: (1) rescue neurons in culture from injury evoked by sodium nitroprusside, hydrogen peroxide (H2O2) and oxygen glucose deprivation; and (2) scavenge reactive oxygen species in vitro. Qualitative and quantitative assessments of cell survival have indicated that: (1) Neuronal cell injury produced following deprivation of oxygen and glucose was significantly attenuated by 5 mu M HU-211. (2) Glial and neuronal cell damage induced by sodium nitroprusside was markedly ameliorated by 10 mu M HU-211. (3) HU-211 reduced protein oxidation initiated by gamma irradiation, and scavenged peroxyl radicals. (4) HU-211 carries an oxidation potential of 550 mV. These findings suggest that HU-211 holds a unique position among putative neuroprotectant agents in that it combines NMDA receptor antagonistic activity and free radical scavenging abilities in a single molecule.
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页码:19 / 29
页数:11
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