Biased mu-opioid receptor ligands: a promising new generation of pain therapeutics
Biased mu-opioid receptor ligands: a promising new generation of pain therapeutics
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DOI：
10.1016/j.coph.2016.11.007
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发表时间：
2017-02-01
影响因子：
4
通讯作者：
Violin, Jonathan D.
中科院分区：
文献类型：
--
作者：
Siuda, Edward R.;Carr, Richard, III;Violin, Jonathan D.
阿片化学和生物学在药理学和医学史上占有举足轻重的地位。吗啡在缓解急性疼痛方面提供了无与伦比的疗效，但也与许多不良副作用有关。G蛋白偶联受体的偏向激动剂的出现扩展了我们对细胞内信号传递的理解，并强调了某些配体能够以不同的方式调节下游通路的概念。靶向一种途径而不是另一种途径的能力使得有偏见的配体的开发具有强大的临床疗效和较少的不良事件。在这篇综述中，我们总结了这些概念，强调了偏倚的u阿片受体药理学，并强调了阿片类药物药理学的发展。
Opioid chemistry and biology occupy a pivotal place in the history of pharmacology and medicine. Morphine offers unmatched efficacy in alleviating acute pain, but is also associated with a host of adverse side effects. The advent of biased agonism at G protein-coupled receptors has expanded our understanding of intracellular signaling and highlighted the concept that certain ligands are able to differentially modulate downstream pathways. The ability to target one pathway over another has allowed for the development of biased ligands with robust clinical efficacy and fewer adverse events. In this review we summarize these concepts with an emphasis on biased mu opioid receptor pharmacology and highlight how far opioid pharmacology has evolved.