Dexanabinol; a novel neuroprotective drug in experimental focal cerebral ischemia

The permanent middle cerebral artery occlusion (PMCAO) model was used to investigate the cerebroprotective effects of the synthetic cannabinoid, dexanabinol (HU-211). Dexanabinol is a noncompetitive N-methyl-D-aspartate antagonist, with antioxidant and anti-TNF alpha properties. Twenty hypertensive rats were subjected to PMCAO. Eight were given 4 mg/kg dexanabinol, i.v., 1 h after PMCAO, eight received vehicle and four were not injected. Five rats underwent sham surgery. Infaret volumes were assessed, as well as TNF alpha oconcentrations and NOS activity in brain homogenates. Dexanabinol significantly decreased infarct volumes. It also significantly lowered TNFa levels in the ipsilateral hemisphere although not to the level of sham operated rats. No effect could be demonstrated on NOS activity. In conclusion, dexanabinol may be a pluripotent cerebroprotective agent. (C) 1999 Elsevier Science B.V. All rights reserved.