Slow dissociation kinetics of fentanyls and nitazenes correlates with reduced sensitivity to naloxone reversal at the μ-opioid receptor.

ABSTRACT:

Background and purpose

Fentanyls and nitazenes are μ-opioid receptor agonists responsible for a large number of opioid overdose deaths. Here, we determined the potency, dissociation kinetics and antagonism by naloxone at the μ receptor of several fentanyl and nitazene analogues, compared to morphine and DAMGO.

Experimental approach

In vitro assays of G protein activation and signalling and arrestin recruitment were performed. AtT20 cells expressing μ receptors were loaded with a membrane potential dye and changes in fluorescence used to determine agonist potency, dissociation kinetics and susceptibility to antagonism by naloxone. BRET experiments were undertaken in HEK293T cells expressing μ receptors to assess Gi protein activation and β-arrestin 2 recruitment.

Key resul

SUBMITTER: Alhosan N 

PROVIDER: S-EPMC7618119 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature