Synthesis and Pharmacology of a Novel μ-δ Opioid Receptor Heteromer-Selective Agonist Based on the Carfentanyl Template.

ABSTRACT: In this work, we studied a series of carfentanyl amide-based opioid derivatives targeting the mu opioid receptor (μOR) and the delta opioid receptor (δOR) heteromer as a credible novel target in pain management therapy. We identified a lead compound named MP135 that exhibits high G-protein activity at μ-δ heteromers compared to the homomeric δOR or μOR and low β-arrestin2 recruitment activity at all three. Furthermore, MP135 exhibits distinct signaling profile, as compared to the previously identified agonist targeting μ-δ heteromers, CYM51010. Pharmacological characterization of MP135 supports the utility of this compound as a molecule that could be developed as an antinociceptive agent similar to morphine in rodents. In vivo characterization reveals that MP

SUBMITTER: Faouzi A 

PROVIDER: S-EPMC7745089 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature