The non-psychotropic cannabinoid (+)-(3S,4S)-7-hydroxy-delta 6- tetrahydrocannabinol 1,1-dimethylheptyl (HU-211) attenuates N-methyl-D-aspartate receptor-mediated neurotoxicity in primary cultures of rat forebrain.
The non-psychotropic cannabinoid (+)-(3S,4S)-7-hydroxy-delta 6- tetrahydrocannabinol 1,1-dimethylheptyl (HU-211), a stereoselective inhibitor of the N-methyl-D-aspartate (NMDA) receptor, protects primary cultures of rat forebrain against NMDA receptor-mediated neurotoxicity. Cell mortality produced by exposure for 10 min to NMDA or glutamate was reduced to approximately 18 or 27%, respectively, by application of 50 microM HU-211 for 10-15 min during or after exposure of cultures to excitatory amino acid. This effect of HU-211 was dependent on its concentration (EC50 = 8.7 +/- 4 microM). HU-211 also reduced the toxicity induced by brief exposure (10 min) to kinase or quisqualate, though less effectively. HU-211 may therefore prove useful as a non-psychoactive drug that protects against neurotoxicity mediated by the NMDA receptor.
Nadler
V
V
Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel Aviv University, Israel.
Mechoulam
R
R
Sokolovsky
M
M
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D016291:Dizocilpine Maleate / Q000494:pharmacology; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009474:Neurons / Q000187:drug effects; D010622:Phencyclidine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000633:toxicity; D016548:Prosencephalon / Q000166:cytology* / Q000187:drug effects; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D002121:Calcium Channel Blockers; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D013759:Dronabinol; C012058:tenocyclidine; D007770:L-Lactate Dehydrogenase; D010622:Phencyclidine; C062018:HU 211