Neuroprotective and antioxidant activities of HU-211, a novel NMDA receptor antagonist.
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 microM HU-211. (2) Glial and neuronal cell damage induced by sodium nitroprusside was markedly ameliorated by 10 microM 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.
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002478:Cells, Cultured / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005609:Free Radicals; D005947:Glucose / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000633:toxicity*; D007150:Immunohistochemistry; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009599:Nitroprusside / Q000633:toxicity; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D000975:Antioxidants; D005609:Free Radicals; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D009599:Nitroprusside; D016291:Dizocilpine Maleate; D013759:Dronabinol; D006861:Hydrogen Peroxide; D005947:Glucose; C062018:HU 211