HU-211, A NON-PSYCHOTROPIC CANNABINOID, RESCUES CORTICAL-NEURONS 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 EC(50) = 3.8 +/- 0.9 mu M. Radioligand binding studies have shown that HU-211 inhibits the binding of [H-3]MK-801 to rat forebrain membranes (K-I = 11.0 mu M +/- 1.323) in a competitive manner, but was unable to displace [H-3]kainate and [H-3]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.