Behavioral pharmacology of methocinnamox: A potential new treatment for opioid overdose and opioid use disorder.
Behavioral pharmacology of methocinnamox: A potential new treatment for opioid overdose and opioid use disorder.
复制标题
甲氧肉桂酸的行为药理学：阿片类药物过量和阿片类药物使用障碍的潜在新疗法。
DOI：
10.1002/jeab.831
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发表时间：
2023
影响因子：
2.7
通讯作者：
France,CharlesP
中科院分区：
文献类型：
--
作者：
Maguire,DavidR;France,CharlesP
阿片类药物过量和阿片类药物使用障碍仍然是公共卫生面临的重大挑战，尽管社会各阶层都提供了有效的药物并作出了重大努力。过去十年中出现了高效力和有效的阿片类药物，如芬太尼及其衍生物，这只会加剧本已严重的问题。行为药理学研究已被证明对于了解药物的效果以及开发和评估涉及中枢神经系统的疾病的药物疗法，包括物质滥用障碍，具有非常重要的价值。本文描述了一种有效、选择性和长效的MU阿片受体拮抗剂美索那莫司的研究计划，并评估其治疗阿片类药物过量和阿片使用障碍的潜力。在啮齿动物和非人类灵长类动物上的研究表明，美洛昔单抗可预防和逆转阿片类药物诱导的呼吸机能抑制，并选择性地阻断阿片类药物的自我给药。这项工作，再加上对甲硫磷神经药理学进行的严格的体外和体外研究，为这种潜在的挽救生命的药物的治疗作用奠定了坚实的基础。此外，这些研究表明，严格的行为药理学研究可以整合到更广泛的药物发现和开发研究计划中。
Opioid overdose and opioid use disorder continue to be significant public health challenges despite the availability of effective medications and significant efforts at all levels of society. The emergence of highly potent and efficacious opioids such as fentanyl and its derivatives over the last decade has only exacerbated what was already a substantial problem. Behavioral pharmacology research has proven invaluable for understanding the effects of drugs as well as developing and evaluating pharmacotherapies for disorders involving the central nervous system, including substance abuse disorders. This paper describes a program of research characterizing a potent, selective, and long‐lasting mu opioid receptor antagonist, methocinnamox, and evaluating its potential for treating opioid overdose and opioid use disorder. Studies in rodents and nonhuman primates demonstrate that methocinnamox prevents and reverses opioid‐induced ventilatory depression and selectively blocks opioid self‐administration. This work, taken together with rigorous in vitro and ex vivo studies investigating methocinnamox neuropharmacology, lays a solid foundation for the therapeutic utility of this potentially life‐saving medication. Moreover, these studies demonstrate how rigorous behavioral pharmacological studies can be integrated in a broader drug discovery and development research program.