Development of HU-211 as a neuroprotectant for ischemic brain damage.
HU-211 (Dexanabinol), a putative neuroprotective agent, was evaluated in a number of animal models including closed head injury, optic nerve crush, global ischemia and focal ischemia. In these models, a single injection of HU-211 given after the insult confers long term functional improvement and significant increase in neuronal survival. Neuroprotective doses of HU-211 were found to be safe in a 14 day toxicological study in two species. In terms of mechanism, the compound behaves as a noncompetitive NMDA antagonist in vitro and in vivo. It blocks NMDA stimulated calcium influx in primary neuronal culture, and head injury related calcium influx in rats. In addition, HU-211 is a potent scavenger of peroxy and hydroxy radicals in vitro and it protects cultured neurons from toxicity of radical generators. Thus, Dexanabinol holds a unique position among putative neuroprotective agents since it combines NMDA blocking activity and free radical scavenging properties in one molecule. These observations support the development of HU-211 as a novel, multiple-action treatment approach for brain damage associated with stroke, cardiac arrest and trauma.
D000818:Animals; D001930:Brain Injuries / Q000517:prevention & control*; D002545:Brain Ischemia / Q000188:drug therapy*; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D005849:Gerbillinae; D016489:Head Injuries, Closed / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D013759:Dronabinol; C062018:HU 211