HU-211, A NON-PSYCHOTROPIC CANNABINOID, RESCUES CORTICAL-NEURONS FROM EXCITATORY AMINO-ACID TOXICITY IN CULTURE

被引:60
作者
ESHHAR, N
STRIEM, S
BIEGON, A
机构
[1] Pharmos Limited, Pharmacology Department, KiryatWeizmann, Rehovot
[2] Pharmos Limited, Pharmacology Department, KiryatWeizmann, Rehovot
关键词
CORTICAL CELL CULTURES; NEUROPROTECTION; EXCITOTOXICITY; CANNABINOID; RAT BRAIN; NMDA RECEPTOR; NMDA ANTAGONIST;
D O I
10.1097/00001756-199312000-00013
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
THE present study examined potential neuroprotective effects of HU-211, a synthetic non-psychotropic cannabinoid with non-competitive NMDA antagonist properties on neurones exposed to various excitotoxins in culture. HU-211 was found to protect neurones from NMDA and quisqualate-induced toxicity but not that produced by AMPA or kainate. NMDA-mediated neurotoxicity was blocked by HU-211 in a dose dependent manner with an EC(50) = 3.8 +/- 0.9 mu M. Radioligand binding studies have shown that HU-211 inhibits the binding of [H-3]MK-801 to rat forebrain membranes (K-I = 11.0 mu M +/- 1.323) in a competitive manner, but was unable to displace [H-3]kainate and [H-3]AMPA binding. These data suggest that the neuroprotective activity of HU-211 is directly associated with the NMDA receptor channel and possibly with the quisqualate receptor of the metabotropic class. Thus, HU-211 appears to act as an NMDA open channel blocker and shows promise as a novel neuroprotectant for clinical use.
引用
收藏
页码:237 / 240
页数:4
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