Ehrlich Aliza T, Darcq Emmanuel
Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, CA, USA.
Department of Psychiatry, Douglas Research Center, McGill University, Montréal, Canada.
Fac Rev. 2021 Feb 19;10:15. doi: 10.12703/r/10-15. eCollection 2021.
Opioids are powerful drugs used by humans for centuries to relieve pain and are still frequently used as pain treatment in current clinical practice. Medicinal opioids primarily target the mu opioid receptor (MOR), and MOR activation produces unmatched pain-alleviating properties, as well as side effects such as strong rewarding effects, and thus abuse potential, and respiratory depression contributing to death during overdose. Therefore, the ultimate goal is to create opioid pain-relievers with reduced respiratory depression and thus fewer chances of lethality. Efforts are also underway to reduce the euphoric effects of opioids and avoid abuse liability. In this review, recent advances in basic science methodology used to understand MOR pharmacology and activities will be summarized. The focus of the review will be to describe current technological advances that enable the study of opioid analgesics from subcellular mechanisms to mesoscale network responses. These advances in understanding MOR physiological responses will help to improve knowledge and future design of opioid analgesics.
阿片类药物是人类数百年来用于缓解疼痛的强效药物，在当前临床实践中仍经常用作疼痛治疗。药用阿片类药物主要作用于μ阿片受体（MOR），MOR的激活产生无与伦比的止痛特性以及诸如强烈奖赏效应等副作用，因此具有滥用潜力，并且呼吸抑制会导致过量用药时死亡。因此，最终目标是研发出呼吸抑制作用减弱、致死几率降低的阿片类止痛药。人们也在努力降低阿片类药物的欣快感并避免其成瘾性。在本综述中，将总结用于理解MOR药理学和活性的基础科学方法的最新进展。综述的重点将是描述当前的技术进展，这些进展使得能够从亚细胞机制到中尺度网络反应来研究阿片类镇痛药。对MOR生理反应的这些进展将有助于增进对阿片类镇痛药的了解并指导未来的设计。
