HU-211, a non-psychotropic cannabinoid, rescues cortical neurones from excitatory amino acid toxicity in culture.
The present study examined potential neuroprotective effects of HU-211, a synthetic non-psychotropic cannabinoid with non-competitive NMDA antagonist properties on neurones exposed to various excitotoxins in culture. HU-211 was found to protect neurones from NMDA and quisqualate-induced toxicity but not that produced by AMPA or kainate. NMDA-mediated neurotoxicity was blocked by HU-211 in a dose dependent manner with an EC50 = 3.8 +/- 0.9 microM. Radioligand binding studies have shown that HU-211 inhibits the binding of [3H]MK-801 to rat forebrain membranes (KI = 11.0 microM +/- 1.323) in a competitive manner, but was unable to displace [3H]kainate and [3H]AMPA binding. These data suggest that the neuroprotective activity of HU-211 is directly associated with the NMDA receptor channel and possibly with the quisqualate receptor of the metabotropic class. Thus, HU-211 appears to act as an NMDA open channel blocker and shows promise as a novel neuroprotectant for clinical use.
Eshhar
N
N
Pharmacology Department, Kiryat Weizmann, Rehovot, Israel.
Striem
S
S
Biegon
A
A
D000596:Amino Acids / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000818:Animals; D002186:Cannabinoids / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D016291:Dizocilpine Maleate / Q000493:pharmacokinetics; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000494:pharmacology; D007150:Immunohistochemistry; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects*; D010751:Phosphopyruvate Hydratase / Q000276:immunology / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D000596:Amino Acids; D002186:Cannabinoids; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D013759:Dronabinol; D010751:Phosphopyruvate Hydratase; C062018:HU 211