by Yi Zhang, Qiuxiang Chen, Yuanyuan Zhou, Qingjun Zeng, Haishan Cui, Yukai Zhou Background G protein-biased mu-opioid receptor (MOR) agonists such as oliceridine and tegileridine were developed to reduce opioid-related side effects while keeping analgesic efficacy. The US FDA approved oliceridine in 2020 and China NMPA approved tegileridine in January 2024.
Clinical development mainly focused on respiratory depression and gastrointestinal problems, but little attention has been paid to the autonomic nervous system (ANS) effects of these drugs. Traditional opioids change heart rate variability (HRV) and sympathovagal balance mainly through central mechanisms.
It is not clear whether biased agonists show different autonomic profiles compared with traditional opioids. There is an ongoing scientific debate about whether the benefits of these drugs come from true signaling bias or from low intrinsic efficacy.
Methods We will conduct a scoping review following JBI methodology and report according to PRISMA-ScR guidelines. We will search PubMed, Embase, Web of Science and Cochrane Library from database start to March 2026.
FDA and NMPA regulatory documents will also be searched. Two reviewers will screen studies and extract data independently.
PLOS ONE (Medicine) published a clinical update in Research Highlights on 15 May 2026.
The item focuses on Autonomic nervous system modulation by G protein-biased mu-opioid receptor agonists: A translational scoping review protocol.
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