Drug design, development and therapy
Clinical Evaluation of Biased μ-Opioid Receptor Agonists: A Narrative Comparative Review from Oliceridine to Tegileridine and Mechanistic Reappraisal
By Xu H, Wang Y, Hu N and 3 others.
Abstract
Background
Managing moderate-to-severe postoperative pain remains a major clinical challenge. Traditional opioids are constrained by dose-limiting opioid-related adverse events (ORAEs), including respiratory depression, nausea, vomiting, and constipation.
Objective
Biased μ-opioid receptor (MOR) agonists were developed to preferentially activate G-protein signaling, which mediates analgesia, while attenuating β-arrestin-2 recruitment, which has been associated with adverse effects. This review narratively compares the translational pharmacology, clinical efficacy, safety, and mechanistic uncertainty of the two approved biased MOR agonists, oliceridine (US FDA, 2020) and tegileridine (China NMPA, 2024).