Open AccessFlucrypyrim, a novel uterine relaxant, has antinociceptive and anti-inflammatory effects in vivo
Author(s) -
Zhongtang Li,
Limei Wang,
YuSheng Cong,
Lin Guo,
Xiaohui Lin,
Zu-Yin Yu,
Xingan Wu,
Jun-Xing Dong,
RiFang Yang,
Yang Cong
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep42040
Subject(s) - in vivo , chemistry , endocrinology , pharmacology , contraction (grammar) , oxytocin , acetylcholine , prostaglandin , uterine contraction , medicine , dephosphorylation , uterine horns , myometrium , protein tyrosine phosphatase , uterus , phosphorylation , phosphatase , biology , biochemistry , microbiology and biotechnology
Consequences of primary dsysmenorrhea (PD) can be severe. Increased prostaglandin production leads to uterine contraction and insufficient blood flow to the endometrium causing ischemia and pain symptoms. Protein tyrosine kinase/phosphatase activities contribute to the modulation of uterine contraction. In our previous study, we found the synthetic β-methoxyacrylates compound Fluacrypyrim (FAPM), significantly increased protein tyrosine phosphatases (PTPs) activity, resulting in dephosphorylation of tyrosine kinases. In the present study, we found that FAPM near completely inhibited prostaglandin F2α (PGF 2α )-, oxytocin-, acetylcholine-, and high K + -induced uterine contractions in rats in vitro, and decreased rat myometrial myosin light chain (MLC 20 ) phosphorylation induced by PGF 2α . A structure–activity relationship assay indicated that the β-methoxyacrylates structure of FAPM is crucial for the inhibition of PGF 2α -induced uterine contractions. FAPM caused a concentration-dependent parallel rightward shift of the concentration–response curve induced by oxytocin, dose-dependently reduced the number of abdominal constrictions and increased the latency time in PGF 2α - and acetic acid-induced writhing test in mice in vivo . Furthermore, FAPM considerably inhibited the development of Carr-induced rat paw edemas and thexylene-induced mouse ear edemas. Taken together, our results indicate that FAPM exerts antinociceptive and anti-inflammatory effects in vivo with considerable potential as a novel uterine relaxant.