Ribeiro João Marcelo Lamim, Filizola Marta
Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
Front Mol Neurosci. 2019 Aug 23;12:207. doi: 10.3389/fnmol.2019.00207. eCollection 2019.
Effective treatments for pain management remain elusive due to the dangerous side-effects of current gold-standard opioid analgesics, including the respiratory depression that has led to skyrocketing death rates from opioid overdoses over the past decade. In an attempt to address the horrific opioid crisis worldwide, the National Institute on Drug Abuse has recently proposed boosting research on specific pharmacological mechanisms mediated by a number of G protein-coupled receptors (GPCRs). This research is expected to expedite the discovery of medications for opioid overdose and opioid use disorders, leading toward a safer and more effective treatment of pain. Here, we review mechanistic insights from recent all-atom molecular dynamics simulations of a specific subset of GPCRs for which high-resolution experimental structures are available, including opioid, cannabinoid, orexin, metabotropic glutamate, and dopamine receptor subtypes.
由于目前的金标准阿片类镇痛药存在危险的副作用，包括导致过去十年阿片类药物过量致死率飙升的呼吸抑制，有效的疼痛管理治疗方法仍然难以捉摸。为了解决全球范围内可怕的阿片类药物危机，美国国家药物滥用研究所最近提议加强对由多种G蛋白偶联受体（GPCR）介导的特定药理机制的研究。这项研究有望加快阿片类药物过量和阿片类药物使用障碍药物的发现，从而实现更安全、更有效的疼痛治疗。在此，我们回顾了最近对特定GPCR子集进行的全原子分子动力学模拟的机制见解，这些GPCR具有高分辨率实验结构，包括阿片类、大麻素类、食欲素类、代谢型谷氨酸类和多巴胺受体亚型。
