Neuroprotective activity of HU-211, a novel NMDA antagonist, in global ischemia in gerbils

Abstract

HU-211, a nonpsychotropic cannabinoid and a noncompetitive NMDA antagonist, was tested in a global ischemia model in the Mongolian gerbil. Male Mongolian gerbils underwent a 10-min bilateral common carotid artery occlusion. HU-211, administered i.v. at 4 mg/kg, 30 min postischemia, induced statistically significant neuroprotection of the CA1 subfield of the hippocampus. A dose-response study demonstrated an inverted U curve in which the 4 mg/kg dose induced the best neuroprotection in the CA1 subfield of the hippocampus (p < 0.05 ANOVA followed by Duncan's post-hoc test). The therapeutic window was then investigated, and in another study, HU-211 4 mg/kg were administered i.v. at 30, 60, 120, and 180 min postinsult. A statistically significant neuroprotection was detected at 30 and 60 min administration postinsult.