Reversing the toxic effects of drugs of abuse

逆转滥用药物的毒性作用

• 批准号: 7221968
• 负责人: ANDREW COOP
• 金额: $ 10.54万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7221968
• 关键词: Reversing; toxic; effects; drugs; abuse

DESCRIPTION (provided by applicant): This proposal represents an application for a Research Career Award (K02) focused on the candidate's long-term goal of developing agents, which attenuate the toxic effects of drugs of abuse. The approach to achieving this goal is to have a research program that seeks to solve problems associated with drug abuse and dependence through testing hypotheses with chemistry-based approaches. The proposed research plan comprises of three projects, sharing the common theme of developing agents to attenuate the potentially lethal effects of drugs of abuse. In the case of opioids, the goal is to develop morphine-like analgesics which do not give rise to the severe constipation seen with current agents; for cocaine, the goal is to develop sigma receptor-based agents as potential treatments for cocaine overdose; for GHB, the goal is to develop a treatment for GHB overdose based on a mixed profile of GHB and GABA-B antagonism. My short-term approach to the latter two goals is to develop the current collaborations with Drs. France and Matsumoto to a point where I am able to take the lead as PI on new R01 submissions. My plans for the opioids is to develop a new research program based on pharmacokinetic mechanisms of tolerance, and initially submit an R21 application to gain valuable preliminary data. This approach is based on the hypothesis that as tolerance is reduced, the ever-increasing doses of morphine (which leads to the constipation) will not be required. My long-tern career goal is to develop these projects and my collaborations to the point where I am able to translate these medications into the clinic or emergency room. The candidate will spend 75% of his time on NIH-funded research. This award will allow the candidate to be relieved from many teaching and administrative responsibilities, thereby allowing him to focus on current and future research projects.

描述（由申请人提供）： 该提案代表了研究职业奖（K02）的申请，该奖项的重点是候选人的长期目标，该目标减弱了滥用药物的毒性作用。实现这一目标的方法是制定一项研究计划，该计划试图通过使用基于化学的方法测试假设来解决与药物滥用和依赖相关的问题。拟议的研究计划包括三个项目，共享开发代理商的共同主题，以减轻滥用药物的潜在致命作用。就阿片类药物而言，目标是发展吗啡样镇痛药，不会引起当前药物看到的严重便秘。对于可卡因而言，目标是开发基于Sigma受体的药物作为可卡因过量的潜在治疗方法。对于GHB，目标是根据GHB和GABA-B拮抗作用的混合曲线开发GHB过量的治疗方法。我对后两个目标的短期方法是开发与DRS的当前合作。法国和松本达到了我能够在新的R01提交中以PI为pi的地步。我对阿片类药物的计划是基于耐受性的药代动力学机制制定新的研究计划，并最初提交R21应用程序以获取有价值的初步数据。这种方法是基于以下假设：随着公差的降低，不需要吗啡剂量（导致便秘）的剂量不断增加。我的长期职业目标是开发这些项目和合作，以至于我能够将这些药物转化为诊所或急诊室。候选人将花费75％的时间在NIH资助的研究上。该奖项将使候选人可以免除许多教学和行政责任，从而使他可以专注于当前和未来的研究项目。