Mu-Opioid receptor biased ligands: A safer and painless discovery of analgesics?
Por:
Madariaga-Mazon, Abraham, Marmolejo-Valencia, Andres F., Li, Yangmei, Toll, Lawrence, Houghten, Richard A., Martinez-Mayorga, Karina
Publicada:
1 nov 2017
Resumen:
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 mu, opioid receptor (R-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 mu-OR agonists have
been reported to selectively activate the G(i) over beta-arrestin
signaling pathway, resulting in lower gastrointestinal dysfunction and
respiratory suppression. Here, we discuss the strategies that led to the
development of biased mu,-OR agonists, and potential areas for
improvement, with an emphasis on structural aspects of the
ligand-receptor recognition process.
Filiaciones:
Madariaga-Mazon, Abraham:
Univ Nacl Autonoma Mexico, Inst Quim, Av Univ 3000, Mexico City 04510, DF, Mexico
Marmolejo-Valencia, Andres F.:
Univ Nacl Autonoma Mexico, Inst Quim, Av Univ 3000, Mexico City 04510, DF, Mexico
Li, Yangmei:
Torrey Pines Inst Mol Studies, 11350 SW Village Pkwy, Port St Lucie, FL 34987 USA
Toll, Lawrence:
Torrey Pines Inst Mol Studies, 11350 SW Village Pkwy, Port St Lucie, FL 34987 USA
Houghten, Richard A.:
Torrey Pines Inst Mol Studies, 11350 SW Village Pkwy, Port St Lucie, FL 34987 USA
Martinez-Mayorga, Karina:
Univ Nacl Autonoma Mexico, Inst Quim, Av Univ 3000, Mexico City 04510, DF, Mexico
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