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

MCAM是一种新的阿片类拮抗剂，其相对于纳洛酮治疗阿片类药物过量的优势包括 与µ阿片受体的假不可逆相互作用，以及更长的作用时间。这些 属性表明更好地逆转非常有效和/或非常长时间的呼吸抑制效果 持久的阿片受体激动剂和更好的阿片使用障碍治疗。中的概念验证研究 非人灵长类动物展示了MCAM对强化和 瑞芬太尼和海洛因分别有呼吸抑制作用。MCAM的剂量为10 比起u阿片受体激动剂的保护作用的倍数没有任何作用。 对恒河猴的食物维持反应，没有改变血压、心率或 体温。 该提案寻求为MCAM(UG3)的组成和药效学研究提供资金 部分)。在UH3部分，GMP-MCAM将在额外的药效学分析和 动物毒性和安全性研究。在与FDA协商后，将寻求IND申请 使用这些数据。 已经为提案的每个阶段确定了合同研究组织。这项建议 描述了建立MCAM安全性和拮抗性的充要条件 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 在人类中的作用时间比任何其他强烈使用的拮抗剂都要长。MCAM提供了潜力 其他任何药物都无法达到的治疗目标。成功地执行了这项任务 提案将确立这些主张。

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.