Methocinnamox (MCAM): A novel õ-opioid receptor antagonist for opioid use disorders

Methocinnamox (MCAM)：一种新型 α-阿片受体拮抗剂，用于治疗阿片类药物使用障碍

• 批准号: 10763458
• 负责人: CHARLES P FRANCE
• 金额: $ 421.81万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-30 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10763458
• 关键词: Methocinnamox; MCAM; novel; opioid; receptor

MCAM is a novel opioid antagonist whose advantages over naloxone for opioid overdose include a pseudo-irreversible interaction with the µ opioid receptor, and a much longer duration of action. These attributes indicate better reversal of the respiratory depressant effects of very potent and/or very long lasting opioid receptor agonists and better treatment of opioid use disorder. Proof-of-concept studies in non human primates demonstrate MCAM’s long duration of action against the reinforcing and respiratory-depressant effects of remifentanil and heroin, respectively. Doses of MCAM that were 10 times larger than those that protected against the effects of mu opioid receptor agonists had no effect on food-maintained responding in rhesus monkeys, and did not modify blood pressure, heart rate or body temperature. This proposal seeks funding for composition and study of the pharmacodynamics of MCAM (UG3 portion). In the UH3 portion, GMP-MCAM will be studied in additional pharmacodynamics assays and animal toxicity and safety studies. An IND application, following consultation with the FDA will be sought using these data. Contract Research Organizations have been identified for each stage of the proposal. The proposal describes the necessary and sufficient conditions from which to establish MCAM’s safety and antagonist activity in animals and humans. MCAM may be able to prevent all actions of any μ-receptor opioid drug in humans for a longer period of time than any other antagonist given acutely. MCAM offers potential therapeutic objectives that are not achieved with any other drug. The successful execution of this proposal will establish these claims.

MCAM 是一种新型阿片拮抗剂，在治疗阿片类药物过量时，其优势包括 与μ阿片受体的伪不可逆相互作用，并且作用持续时间更长。这些 属性表明可以更好地逆转非常有效和/或非常长的呼吸抑制作用 持久的阿片受体激动剂和更好的治疗阿片类药物使用障碍。概念验证研究 非人类灵长类动物证明了 MCAM 对增强和增强作用的长期作用 瑞芬太尼和海洛因分别具有呼吸抑制作用。 MCAM 剂量为 10 比那些可以防止μ阿片受体激动剂作用的药物大几倍，但没有效果 恒河猴的食物维持反应，并且没有改变血压、心率或 体温。 该提案寻求资金用于 MCAM 的组成和药效学研究（UG3 部分）。在 UH3 部分中，将在额外的药效学测定中研究 GMP-MCAM 动物毒性和安全性研究。与 FDA 协商后将寻求 IND 申请 使用这些数据。 已为该提案的每个阶段确定了合同研究组织。提案 描述了建立 MCAM 的安全性和拮抗性的充分必要条件 动物和人类的活动。 MCAM 可能能够阻止任何μ受体阿片类药物的所有作用 在人体中的作用时间比任何其他急性给予的拮抗剂更长。 MCAM 提供潜力 任何其他药物都无法达到的治疗目标。此次成功执行 提案将证实这些主张。