Optimization of a Series of Mu Opioid Receptor (MOR) Agonists with High G Protein Signaling Bias.

ABSTRACT: While mu opioid receptor (MOR) agonists are especially effective as broad-spectrum pain relievers, it has been exceptionally difficult to achieve a clear separation of analgesia from many problematic side effects. Recently, many groups have sought MOR agonists that induce minimal βarrestin-mediated signaling because MOR agonist-treated βarrestin2 knockout mice were found to display enhanced antinociceptive effects with significantly less respiratory depression and tachyphylaxis. Substantial data now exists to support the premise that G protein signaling biased MOR agonists can be effective analgesic agents. We recently showed that, within a chemical series, the degree of bias correlates linearly with the magnitude of the respiratory safety index. Herein we describe the synthesis and optimi

SUBMITTER: Kennedy NM 

PROVIDER: S-EPMC6386185 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature