Low Intrinsic Efficacy Alone Cannot Explain the Improved Side Effect Profiles of New Opioid Agonists.

ABSTRACT: In a recent report in Science Signaling (Gillis, A., et al. Low intrinsic efficacy for G protein activation can explain the improved side effect profiles of new opioid agonists. Sci. Signaling 2020, 13, eaaz3140 10.1126/scisignal.aaz3140), it was suggested that low intrinsic agonism, and not biased agonism, leads to an improvement in the separation of potency in opioid-induced respiratory suppression versus antinociception. Although many of the compounds that were tested have been shown to display G protein signaling bias in prior publications, the authors conclude that because they cannot detect biased agonism in their cellular signaling studies the compounds are therefore not biased agonists. Rather, they conclude that it is low intrinsic efficacy that leads to the therapeu

SUBMITTER: Stahl EL 

PROVIDER: S-EPMC8885792 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature