COMPARATIVE BRAIN METABOLISM-A DRUG DEVELOPMENT TOOL

比较脑代谢-药物开发工具

• 批准号: 2714279
• 负责人: TERRY F BROWN
• 金额: $ 10万
• 依托单位: MIICRO, INC
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2714279
• 关键词: antidepressants; bioimaging /biomedical imaging; brain mapping; brain metabolism; bupropion; clinical research; clinical trials; drug metabolism; drug screening /evaluation; fluoxetine; glucose metabolism; human subject; neuropharmacology; positron emission tomography; psychopharmacology

APPLICANT'S DESCRIPTION: Modification of regional brain glucose metabolism has been shown to occur with different classes of psychopharmacological compound. Different sites of localization and quantitative effects have been demonstrated using PET under controlled behavioral conditions. We propose to examine the sensitivity of this method by a within-class comparison of three antidepressant drugs in a placebo, double-blind, counterbalanced controlled study in human subjects. The basis of the study will be to generate statistically mapped brain images in common coordinate space, thus enabling neuroanatomic localization of the metabolic end effects of each drug to be identified. Previously acquired data demonstrating the metabolic changes produced by fluoxetine will be compared to venlafaxine and bupropion. We hypothesize that all three drugs will share a main effect in the limbic system, and in addition, venlafaxine and bupropion will show discernibly different metabolic end effects based on their specific mechanism of action. This approach represents a potentially significant contribution to drug development in clinical trials. In a cost-effective and efficient manner, it can provide predictive value for assessing brain effect and site effect profiles of new chemical entities and direct comparison with established within-class clinically effective drugs. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE

申请人的描述：已证明不同类别的精神药理学化合物会发生区域脑葡萄糖代谢的改变。已在受控行为条件下使用 PET 证明了不同位点的定位和定量效应。我们建议通过在人类受试者中进行的安慰剂、双盲、平衡对照研究中对三种抗抑郁药物进行组内比较来检验该方法的敏感性。该研究的基础是在公共坐标空间中生成统计映射的大脑图像，从而能够识别每种药物代谢最终效应的神经解剖学定位。先前获得的数据表明氟西汀产生的代谢变化将与文拉法辛和安非他酮进行比较。我们假设所有三种药物都将在边缘系统中发挥主要作用，此外，文拉法辛和安非他酮根据其具体的作用机制将显示出明显不同的代谢最终效应。这种方法对临床试验中的药物开发具有潜在的重大贡献。它可以以经济有效的方式提供预测价值，用于评估新化学实体的脑效应和位点效应概况，并与现有的同类临床有效药物进行直接比较。 拟议的商业应用：不可用