New Opioids for Alcoholism

治疗酗酒的新阿片类药物

• 批准号: 7052209
• 负责人: John R Cashman
• 金额: $ 16.15万
• 依托单位: BEHAVIORAL PHARMA, INC.
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7052209
• 关键词: alcoholic beverage consumption; alcoholism /alcohol abuse; alcoholism /alcohol abuse therapy; alcoholism antagonist; analog; behavior test; chemical synthesis; dimethylsulfoxide; disease /disorder model; drug adverse effect; drug design /synthesis /production; drug discovery /isolation; drug metabolism; drug screening /evaluation; ethanol; high performance liquid chromatography; laboratory rat; opioid receptor

DESCRIPTION (provided by applicant): Highly potent, orally active, metabolically stable, long-lived opioid agents for the treatment of alcoholism that have decreased side effects such as nausea, addiction liability, immunosuppression and respiratory depression represents a great unmet need. While a mu opioid receptor antagonist is currently approved by the FDA for alcoholism, it possesses several drawbacks. Recently, human clinical trials have shown that a new class of opioid with an improved side effect profile is available. In this Phase I proposal, efficacious congeners of these novel opioids specifically designed to be antagonists of the mu opioid receptor will be optimized by medicinal chemistry and tested in vitro and in vivo for pharmacological activity. Medicinal chemistry proposed herein for Phase I will lead to additional lead optimization of the most efficacious drug candidates identified previously. The Aims of this proposal include: 1) Test the feasibility of the currently available novel opioid antagonists to decrease alcohol consumption in an animal model, 2) Optimize the pharmacological activity and 3) Maximize the preclinical safety of the most promising drug candidates. After the successful completion of this work, more extensive testing of drug candidate compounds will be done in animals in Phase II. The goal of our feasibility work is to show that efficacious and safe agents can be observed in animal models based on our in vitro data. We expect that development of the proposed novel anti-alcoholism drug candidates will provide new agents useful in the future amelioration of human suffering and economical loss. Anti-alcoholism medication, animal models, drug development, opioid drug evaluation. The need for potent, orally active, metabolically stable, long-lived medication to address alcohol abuse is immense. Procurement of a long-lasting oral anti-alcoholism medication that has an improved side effect profile compared with agents currently in use will provide a therapeutic that is currently not available. The potential commercial application of the work is that the research could lead to a 'blockbuster' drug product.

描述（由申请人提供）：用于治疗酗酒的高效、口服活性、代谢稳定、长效的阿片类药物，可减少恶心、成瘾倾向、免疫抑制和呼吸抑制等副作用，这是一个巨大的未满足的需求。虽然 mu 阿片受体拮抗剂目前已被 FDA 批准用于治疗酗酒，但它有几个缺点。最近，人体临床试验表明，一种新型阿片类药物的副作用得到了改善。在此一期提案中，这些专门设计为 mu 阿片受体拮抗剂的新型阿片类药物的有效同系物将通过药物化学进行优化，并在体外和体内测试药理活性。本文提出的第一阶段药物化学将导致对先前确定的最有效的候选药物进行额外的先导优化。该提案的目标包括：1）测试目前可用的新型阿片拮抗剂在动物模型中减少酒精消耗的可行性，2）优化药理活性，3）最大限度地提高最有前途的候选药物的临床前安全性。这项工作成功完成后，第二阶段将在动物身上对候选药物化合物进行更广泛的测试。我们可行性工作的目标是证明根据我们的体外数据，可以在动物模型中观察到有效且安全的药物。我们期望所提出的新型抗酒精中毒候选药物的开发将提供可用于未来改善人类痛苦和经济损失的新药物。抗酒精中毒药物、动物模型、药物开发、阿片类药物评价。解决酒精滥用问题需要有效的、口服活性的、代谢稳定的、长效的药物。采购一种与目前使用的药物相比具有改善的副作用的长效口服抗酒精药物将提供目前无法获得的治疗方法。这项工作的潜在商业应用是该研究可能会产生一种“重磅炸弹”药品。