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

@article{Dewire2013AGP,
  title={A G Protein-Biased Ligand at the $\mu$-Opioid Receptor Is Potently Analgesic with Reduced Gastrointestinal and Respiratory Dysfunction Compared with Morphine},
  author={S. Dewire and D. Yamashita and D. Rominger and G. Liu and C. Cowan and T. Graczyk and Xiao-tao Chen and P. Pitis and D. Gotchev and C. Yuan and Michael Koblish and M. Lark and J. D. Violin},
  journal={The Journal of Pharmacology and Experimental Therapeutics},
  year={2013},
  volume={344},
  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… Expand

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