Mu-Opioid receptor biased ligands: A safer and painless discovery of analgesics?
Article
Madariaga-Mazón, A, Marmolejo-Valencia, AF, Li, Y et al. (2017). Mu-Opioid receptor biased ligands: A safer and painless discovery of analgesics?
. DRUG DISCOVERY TODAY, 22(11), 1719-1729. 10.1016/j.drudis.2017.07.002
Madariaga-Mazón, A, Marmolejo-Valencia, AF, Li, Y et al. (2017). Mu-Opioid receptor biased ligands: A safer and painless discovery of analgesics?
. DRUG DISCOVERY TODAY, 22(11), 1719-1729. 10.1016/j.drudis.2017.07.002
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.
