The overall goal of this project is to develop a novel therapy for neurological injury. The concept is to combine two mechanisms known to provide neuroprotection from ischemic damage. Thus, we will combine a nitrone, known to have potent free radical scavenging activity with memantine, an open channel, uncompetitive NMDA receptor inhibitor, with demonstrated neuroprotective benefit in human clinical trials. In this proposal, we will synthesize novel dual functional memantine nitrones, demonstrate their neuroprotective effects both in vitro and in a rodent cerebral ischemia mice model. Based on these studies we are confident that this work will produce neuroprotective agents useful in neurodegenerative conditions such as stroke, epilepsy, trauma, and Alzheimer's disease, in addition to AIDS dementia. PROPOSED COMMERCIAL APPLICATION: A novel drug therapy for ischemia/stroke has a substantial commercial market.