Anti-ischemia activity of HU-211, a non-psychotropic synthetic cannabinoid.
The novel tricyclic-terpenoid type cannabinoid, HU-211, was tested in gerbils and rats for protection against the effects of cerebral ischemia. Our transient ischemic models in gerbils and rats are based on the protection afforded against the lethal effects of global ischemia. HU-211 gave over 30% protection, by i.v. administration. The optimal dose ranges of HU-211 were between 5 and 10 mg/kg i.v. In gerbils we used a transient ischemia model induced by occlusion (10 min) of the bilateral common carotid arteries (BCCA). HU-211, 8 mg/kg i.v., gave a significantly (p < or = 0.05) better in vivo performed than a control group over three days following ischemia. Histology performed in gerbil model also resulted in significantly (p < 0.001) diminished degeneration area of CA1 in the hippocampus after treatment of HU-211. In the rat model, after four vessel occlusion (4VO) (20 min), HU-211 treatment significantly (p < 0.01) improved neurobehavior scoring. These results show that the new synthetic cannabinoid can protect against hippocampal neuron damage due to selective brain injury induced by cerebral global ischemia in gerbils or rats.
Pharmos Ltd., Kiryat Weizmann, Rehovot, Israel.
M
M
Vered
A
A
Bar-Joseph
L
L
Belayev
Y
Y
Berkovich
A
A
Biegon
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology; D001929:Brain Edema / Q000473:pathology*; D002545:Brain Ischemia / Q000473:pathology*; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005849:Gerbillinae; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D007275:Injections, Intravenous; D002546:Ischemic Attack, Transient / Q000473:pathology; D008297:Male; D009410:Nerve Degeneration / Q000187:drug effects; D009460:Neurologic Examination / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D016194:Receptors, N-Methyl-D-Aspartate; D013759:Dronabinol; C062018:HU 211