Flucrypyrim, a novel uterine relaxant, has antinociceptive and anti-inflammatory effects in vivo

• Published in: Scientific reports Vol. 7; no. 1; p. 42040
• Main Authors: Li, Zhongtang, Wang, Limei, Cong, Yue, Guo, Lin, Lin, Xiaohui, Yu, Zuyin, Wu, Xingan, Dong, Junxing, Yang, Rifang, Cong, Yuwen
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 21-02-2017; Nature Publishing Group
• Subjects: 13; 13/106; 13/95; 631/154/436/2387; 692/308/153; Acetic acid; Acetylcholine; Acrylates - pharmacology; Analgesics - pharmacology; Animals; Anti-Inflammatory Agents - pharmacology; Blood flow; Contraction; Dephosphorylation; Dinoprost - antagonists & inhibitors; Endometrium; Humanities and Social Sciences; Inflammation; Ischemia; Latency; Mice; multidisciplinary; Myometrium; Myosin; Nociceptive Pain; Oxytocin; Pain; Pain perception; Phosphorylation; Protein-tyrosine kinase; Protein-tyrosine-phosphatase; Pyrimidines - pharmacology; Rats; Rodents; Science; Structure-Activity Relationship; Uterine Contraction - drug effects; Uterus
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep42040

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.