发育毒性
兴奋剂
类阿片
胎儿
止痛药
医学
畸形学
受体
怀孕
内分泌学
生理学
内科学
药理学
生物
遗传学
作者
Bin Liu,Hongyu Chen,Chunmei Li,Yuanyuan Guan,Wanglin Jiang,Hanrong Wang,Wei Guo,Wen Wen,Xiaobo Cen,Hongbo Wang,Jingwei Tian
标识
DOI:10.1016/j.reprotox.2023.108403
摘要
Opioids remain the most powerful analgesics for moderate to severe pain but their clinical use, misuse and abuse has been an alarming medical problem, especially for those users at child-bearing age. Mu-opioid receptor (MOR) biased agonists have been suggested as superior alternatives with better therapeutic ratios. We recently discovered and characterized a novel MOR biased agonist, LPM3480392, which demonstrates robust analgesic effect, favorable pharmacokinetic performance, and mild respiratory suppression in vivo. To understand the safety profile of LPM3480392 on the reproductive system and embryonic development, this study evaluated the effects of LPM3480392 on the fertility and early embryonic development, embryo-fetal development, and pre- and postnatal development in rats. Results showed that LPM3480392 had mild effects on parental male and female animals, accompanied by subtle early embryonic loss and delayed ossification of fetal development during organogenesis period. In addition, although minor effects were found on normal developmental milestones and behaviors in the pups, there was no evidence of malformed effect. In conclusion, these results suggest that LPM3480392 has a favorable safety profile with only minor effects on the reproductive and developmental outcomes in animals, which support the development of LPM3480392 as a novel analgesic.
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