Neuroprotective activity of HU-211, a novel NMDA antagonist, in global ischemia in gerbils.
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.
Bar-Joseph
A
A
Pharmos Corp., Kiryat Weizmann, Rehovot, Israel.
Berkovitch
Y
Y
Adamchik
J
J
Biegon
A
A
D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002545:Brain Ischemia / Q000139:chemically induced* / Q000473:pathology*; D017536:Carotid Artery, Common / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005849:Gerbillinae; D006339:Heart Rate / Q000502:physiology; D006624:Hippocampus / Q000473:pathology; D008297:Male; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D016194:Receptors, N-Methyl-D-Aspartate; D013759:Dronabinol; C062018:HU 211