Novel NMDA Receptor-Binding Drugs for Ischemia/Stroke

治疗缺血/中风的新型 NMDA 受体结合药物

• 批准号: 6550204
• 负责人: YUQIANG WANG
• 金额: $ 10万
• 依托单位: PANORAMA RESEARCH, INC.
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2003-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6550204
• 关键词: NMDA receptors; amantadine; antiparkinson drugs; cerebral ischemia /hypoxia; drug design /synthesis /production; drug screening /evaluation; electrophysiology; free radical scavengers; laboratory mouse; neuroprotectants; nitrone; receptor binding; stroke; voltage /patch clamp

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.

描述(由申请人提供)：这个项目的总体目标是开发一种治疗神经损伤的新疗法。这一概念是将两种已知的提供神经保护免受缺血损伤的机制结合起来。因此，我们将把已知具有强大的自由基清除活性的硝酮与美金刚(一种开放的通道、非竞争性的NMDA受体抑制剂)结合起来，在人类临床试验中证明具有神经保护作用。在这项提议中，我们将合成新的双功能美金刚硝酮，在体外和在啮齿动物脑缺血小鼠模型中展示它们的神经保护作用。基于这些研究，我们相信，除了艾滋病痴呆症之外，这项工作将生产出对中风、癫痫、创伤和阿尔茨海默病等神经退行性疾病有用的神经保护剂。 建议的商业应用： 一种治疗脑缺血/卒中的新型药物疗法具有很大的商业市场。