There currently exists no effective prophylactic or post-hoc pharmacotherapy for minimizing ischemia-induced neuronal damage. More than one million people in America are believed to suffer neuronal damage and physical and cognitive impairments as a consequence of ischemia associated with chronic cerebrovascular disease or acute cardiac arrest. NOVA Pharmaceutical Corporationhas discovered two series of compounds that show particular promise in preliminary screens for cerebroprotective activity; lead compounds increase survival in an hypoxic environment and block NMDA and MES-induced seizures.The primary goal of this research is to confirm the cerebroprotective potential of these agents, using models of transient global (gerbil carotid artery occlusion) and of focal (photochemically induced thrombosis) ischemia. A second goal will be to complete examination of the two series of compounds in the preliminary cerebroprotection screens. Finally, it is planned to evaluate the potency of both series of compounds to displace sigma receptor ligands and to noncompetitively modulate binding at the [3H]TCP-labeled, NMDA receptor-associated "PCP" site in the hope of identifying a binding-site/receptor assay predictive of cerebroprotective activity.Awardee's statement of the potential commercial applications of the research:The potential market includes more than one million people in America suffering neuronal damage and cognitive impairment as a result of thrombic stroke or cardiac arrest. Other possible therapeutic applications include prevention of neuronal damage following perinatal hypoxia, prevention of hypoxic damage during tissue transplantation, and treatment of epilepsy.National Institute of Neurological Disorders and Stroke (NINDS)
