SYNTHETIC NEUROPROTECTIVE GLUTAMATE RELEASE BLOCKERS

合成神经保护谷氨酸释放阻滞剂

• 批准号: 2267723
• 负责人: JAMES B FISCHER
• 金额: $ 25万
• 依托单位: CAMBRIDGE NEUROSCIENCE
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-12-17 至 1995-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2267723
• 关键词: NMDA receptors; aminoacid inhibitor; calcium channel; calcium channel blockers; cerebral ischemia /hypoxia; chemical models; chemical structure function; chemical substitution; conformation; drug design /synthesis /production; drug interactions; drug screening /evaluation; electrophysiology; gerbil /jird; glutamates; guanidines; laboratory rat; molecular biology; neuropharmacology; neuroprotectants; neurotransmitter transport; sodium channel; voltage /patch clamp; voltage gated channel

Brain damage in stroke and in cardiac arrest results from an inadequate supply of blood to the brain, termed brain ischemia. Brain ischemia depletes the energy stores of affected brain regions and causes the excessive release of glutamate and other neurotransmitters from metabolically compromised nerve terminals. Our goal is to discover synthetic, selective antagonists of the ion channels controlling the release of glutamate and other neurotransmitters. Such compounds may be employed as drugs to limit brain damage in focal ischemia (stroke) and global ischemia (resulting from cardiac arrest or complications of cardiac surgery). Using novel drug discovery methology based on a proprietary method for monitoring neurotransmitter release from brain nerve terminals, we have developed a novel compound series of synthetic glutamate release blockers, members of which are highly neuroprotective in an animal model of brain ischemia. During Phase II, we hope to incorporate rational drug design strategies resulting from knowledge on the structure of the site of interaction of these neuroprotective compounds with its ion channel targets. Candidates for drug development are likely to emerge from the Phase II project period, and selection of such candidates is the central goal of the project.

中风和心脏骤停造成的脑损伤是由于缺乏