The <i>in vitro</i> functional profiles of fentanyl and nitazene analogs at the μ-opioid receptor - high efficacy is dangerous regardless of signaling bias.

ABSTRACT: Novel synthetic opioids (NSOs), including both fentanyl and non-fentanyl analogs that act as the μ-opioid receptor (MOR) agonists, are associated with serious intoxication and fatal overdose. Previous studies proposed that G protein biased MOR agonists are safer pain medications, while other evidence indicates that low intrinsic efficacy at MOR better explains reduced opioid side effects. Here, we characterized the in vitro functional profiles of various NSOs at MOR using adenylate cyclase inhibition and β-arrestin2 recruitment assays, in conjunction with the application of the receptor depletion approach. By fitting the concentration-response data to the operational model of agonism, we deduced the intrinsic efficacy and affinity for each opioid in the Gi protein signaling and β-ar

SUBMITTER: Tsai MM 

PROVIDER: S-EPMC10680598 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature