Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8410205 | Drug Discovery Today | 2017 | 16 Pages |
Abstract
Biased activation of G-protein-coupled receptors (GPCRs) is shifting drug discovery efforts and appears promising for the development of safer drugs. The most effective analgesics to treat acute pain are agonists of the μ opioid receptor (μ-OR), a member of the GPCR superfamily. However, the analgesic use of opioid drugs, such as morphine, is hindered by adverse effects. Only a few μ-OR agonists have been reported to selectively activate the Gi over β-arrestin signaling pathway, resulting in lower gastrointestinal dysfunction and respiratory suppression. Here, we discuss the strategies that led to the development of biased μ-OR agonists, and potential areas for improvement, with an emphasis on structural aspects of the ligand-receptor recognition process.
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Authors
Abraham Madariaga-Mazón, Andrés F. Marmolejo-Valencia, Yangmei Li, Lawrence Toll, Richard A. Houghten, Karina Martinez-Mayorga,