HU-211, a nonpsychotropic cannabinoid, produces short- and long-term neuroprotection after optic nerve axotomy.
HU-211 is a novel synthetic analog of tetrahydrocannabinol that was recently shown in animal models to be nonpsychotropic. In this study we show that HU-211 can potentially be used as a neuroprotective compound in the CNS. Using a calibrated crush injury of adult rat optic nerve, we show that HU-211 can reduce injury-induced metabolic and electrophysiological deficits. Energy metabolism was monitored by measuring the intramitochondrial nicotine-amine adenine dinucleotide redox state hourly for 6 h after injury and treatment. Electrophysiological activity was assessed by compound action potential and visual evoked potential response. Beneficial effects were dose-dependent, being optimal at 7 mg/kg, administered intraperitoneally. The time window during which treatment was effective was found to be from the time of injury for at least 5 h, with treatment most effective at the time of injury. These results strongly suggest that HU-211, given immediately after CNS injury at the optimal dosage, may possess neuroprotective activities.
Yoles
E
E
Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
Belkin
M
M
Schwartz
M
M
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001369:Axons; D001930:Brain Injuries / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004334:Drug Administration Schedule; D004594:Electrophysiology / Q000379:methods; D004734:Energy Metabolism / Q000187:drug effects; D005074:Evoked Potentials, Visual / Q000187:drug effects; D008297:Male; D009243:NAD / Q000378:metabolism; D009409:Nerve Crush; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009900:Optic Nerve / Q000502:physiology*; D020221:Optic Nerve Injuries; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D018696:Neuroprotective Agents; D009243:NAD; D013759:Dronabinol; C062018:HU 211