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Mu-Opioid receptor biased ligands: A safer and painless discovery of analgesics?

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 ? opioid receptor (?-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 ?-OR agonists have been reported to selectively activate the Gi over ?-arrestin signaling pathway, resulting in lower gastrointestinal dysfunction and respiratory suppression. Here, we discuss the strategies that led to the development of biased ?-OR agonists, and potential areas for improvement, with an emphasis on structural aspects of the ligand-receptor recognition process.

SUBMITTER: Madariaga-Mazon A

PROVIDER: S-EPMC6620030 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Mu-Opioid receptor biased ligands: A safer and painless discovery of analgesics?

Madariaga-Mazón Abraham A Marmolejo-Valencia Andrés F AF Li Yangmei Y Toll Lawrence L Houghten Richard A RA Martinez-Mayorga Karina K

Drug discovery today 20170722 11

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 G<sub>i</sub> over β-arrestin signaling pathway, resul ...[more]

PMID: 28743488

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