A G Protein-Biased Ligand at the μ-Opioid Receptor Is Potently Analgesic with Reduced Gastrointestinal and Respiratory Dysfunction Compared with Morphine

  title={A G Protein-Biased Ligand at the $\mu$-Opioid Receptor Is Potently Analgesic with Reduced Gastrointestinal and Respiratory Dysfunction Compared with Morphine},
  author={Scott M Dewire and Dennis S. Yamashita and David H. Rominger and Guodong Liu and Conrad L. Cowan and Thomas M. Graczyk and Xiao-tao Chen and Philip M. Pitis and Dimitar B. Gotchev and Catherine C.K. Yuan and Michael Koblish and Michael W. Lark and Jonathan D. Violin},
  journal={The Journal of Pharmacology and Experimental Therapeutics},
  pages={708 - 717}
The concept of ligand bias at G protein-coupled receptors broadens the possibilities for agonist activities and provides the opportunity to develop safer, more selective therapeutics. Morphine pharmacology in β-arrestin-2 knockout mice suggested that a ligand that promotes coupling of the μ-opioid receptor (MOR) to G proteins, but not β-arrestins, would result in higher analgesic efficacy, less gastrointestinal dysfunction, and less respiratory suppression than morphine. Here we report the… 

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