Year: 2026
Type: article
Abstract: Fentanyl is a potent analgesic widely used in clinical practice. Fentanyl and its analogues are seriously abused and are emerging in the illegal drug market, leading to numerous intoxication cases. However, assessment of the potency of the pharmacological effect of these novel fentanyl analogues remains limited and inconsistent across studies. The development of novel analgesics has largely relied on the assessment of mu opioid receptor (MOR) binding affinity, with insufficient verification through the assessment of antinociceptive effects. This study evaluated the antinociceptive effects of 25 fentanyl analogues to investigate the relationship between chemical structure and antinociceptive effect. In this study, hot plate tests were conducted in mice to generate time-effect and dose-effect curves for the evaluation of the antinociceptive effect of fentanyl and its analogues. The results demonstrated that the antinociceptive effects of fentanyl analogues were dose- and time-dependent. The potency of the antinociceptive effect observed in this study generally aligned with the corresponding MOR binding affinities reported in the literature, although several analogues exhibited discrepancies. Structural modifications in different regions of the fentanyl scaffold affect the antinociceptive potency to different degrees, and the duration of action also varied across fentanyl analogues. Furthermore, opioid-induced hyperalgesia (OIH) was observed following administration of several fentanyl analogues, raising potential concerns regarding their abuse liability and development for analgesic purposes. Taken together, this study systematically evaluated and compared the antinociceptive effects of fentanyl analogues. The findings clarify the relationship between chemical structure and the antinociceptive effect, providing valuable insights for drug regulation and the development of novel analgesics.
DOI: 10.3390/ijms27073028
Authors: Yuanyuan Chen, Kaixi Li, Xiangyu Li, Simeng Zhang, Deli Xu, Yawen Xu, Yanling Qiao, Yizhao Xu, Mengchan Xia, Weitao Qin, Bin Di, Peng Xu
Language: English
Subfield: Anesthesiology and Pain Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,499
Awards: G108876304, G7971100408
OpenAlex ID: W7140609511