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

被引：80

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

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 1995年 / 283卷 / 1-3期

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.

引用

页码：19 / 29

页数：11

共 53 条

[21] ANTIOXIDANT ACTIVITY OF CARNOSINE, HOMOCARNOSINE, AND ANSERINE PRESENT IN MUSCLE AND BRAIN [J].

KOHEN, R ;

YAMAMOTO, Y ;

CUNDY, KC ;

AMES, BN .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (09) :3175-3179

[22]

Liebler Daniel C., 1993, P85

[23] PROSPECTS FOR CLINICALLY TOLERATED NMDA ANTAGONISTS - OPEN-CHANNEL BLOCKERS AND ALTERNATIVE REDOX STATES OF NITRIC-OXIDE [J].

LIPTON, SA .

TRENDS IN NEUROSCIENCES, 1993, 16 (12) :527-532

[24] HIPPOCAMPAL-LESIONS INDUCED BY MICROINJECTION OF THE NITRIC-OXIDE DONOR NITROPRUSSIDE [J].

LOIACONO, RE ;

BEART, PM .

EUROPEAN JOURNAL OF PHARMACOLOGY, 1992, 216 (02) :331-333

[25]

LUSTIG HS, 1992, J NEUROCHEM, V59, P2193

[26] NITRIC-OXIDE - A DOWNSTREAM MEDIATOR OF CALCIUM TOXICITY IN THE ISCHEMIC CASCADE [J].

MAIESE, K ;

WAGNER, J ;

BOCCONE, L .

NEUROSCIENCE LETTERS, 1994, 166 (01) :43-47

[27]

MAIESE K, 1993, J NEUROSCI, V13, P3034

[28]

MCCAY PB, 1978, TOCOPHEROL OXYGEN BI, P41

[29]

MCCORD JM, 1969, J BIOL CHEM, V244, P6049

[30] NOVEL PHARMACOLOGICAL THERAPIES IN THE TREATMENT OF EXPERIMENTAL TRAUMATIC BRAIN INJURY - A REVIEW [J].

MCINTOSH, TK .

JOURNAL OF NEUROTRAUMA, 1993, 10 (03) :215-261

← 1 2 3 4 5 6 →