Kun Yi,* Wenjie Sun,* Wen Yu, Shibiao Chen

Department of Anesthesiology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Shibiao Chen, Department of Anesthesiology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 17 Yongwai Zhengjie, Donghu District, Nanchang, Jiangxi Province, 330006, People’s Republic of China, Tel/Fax +862413870982918, Email chenlaoshi1111@163.com

Abstract: Opioids can effectively relieve pain but carry risks of addiction and adverse effects. Oliceridine, a G protein-biased μ-Opioid receptor (MOR) agonist, has emerged as a promising safer alternative. By preferentially activating G-protein-biased agonist targeting the μ-opioid receptor while downregulating β-arrestin2 recruitment, oliceridine (Olinvyk) achieves potent analgesia with reduced incidence of opioid-related adverse effects. Supported by robust preclinical data, oliceridine has demonstrated significant clinical potential, prompting global clinical trials to define its optimal indications and therapeutic scenarios. This review synthesizes current evidence on oliceridine’s efficacy, safety, and mechanistic specificity across diverse surgical settings, contrasting its profile with conventional opioids. Additionally, we discuss future research priorities, including dose optimization, expansion into chronic pain management, and long-term safety evaluation.

Keywords: oliceridine, G protein-biased opioids, pain management, β-arrestin2