Atomic-Level Characterization of the Methadone-Stabilized Active Conformation of µ-Opioid Receptor.

ABSTRACT: Methadone is a synthetic opioid agonist with notoriously unique properties, such as lower abuse liability and induced relief of withdrawal symptoms and drug cravings, despite acting on the same opioid receptors triggered by classic opioids-in particular the µ-opioid receptor (MOR). Its distinct pharmacologic properties, which have recently been attributed to the preferential activation of β-arrestin over G proteins, make methadone a standard-of-care maintenance medication for opioid addiction. Although a recent biophysical study suggests that methadone stabilizes different MOR active conformations from those stabilized by classic opioid drugs or G protein-biased agonists, how this drug modulates the conformational equilibrium of MOR and what specific active conformation of th

SUBMITTER: Kapoor A 

PROVIDER: S-EPMC7562981 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature