Novel NMDA Receptor-Binding Drugs for Ischemia/Stroke

描述（由申请人提供）：本项目的总体目标是开发一种治疗神经损伤的新疗法。其概念是将联合收割机两种已知的机制结合起来，以提供对缺血性损伤的神经保护。因此，我们将结合联合收割机，已知具有有效的自由基清除活性的硝酮与美金刚胺，一种开放通道，非竞争性NMDA受体抑制剂，在人体临床试验中证明具有神经保护益处。本研究拟合成新型双功能美金刚硝酮，并在体外和啮齿动物脑缺血模型中证明其神经保护作用。基于这些研究，我们相信这项工作将产生神经保护剂，可用于神经退行性疾病，如中风，癫痫，创伤和阿尔茨海默病，以及艾滋病痴呆症。 拟定商业应用： 用于缺血/中风的新型药物疗法具有巨大的商业市场。

DESCRIPTION (provided by applicant): 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.