title: Flucrypyrim, a novel uterine relaxant, has antinociceptive and anti-inflammatory effects in vivo.
abstract: 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 (PGF2α)-, oxytocin-, acetylcholine-, and high K+-induced uterine contractions in rats in vitro, and decreased rat myometrial myosin light chain (MLC20) phosphorylation induced by PGF2α. A structure-activity relationship assay indicated that the β-methoxyacrylates structure of FAPM is crucial for the inhibition of PGF2α-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 PGF2α- 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.
authors.affiliation: Department of Pathophysiology, Beijing Institute of Radiation Medicine, Beijing, China.|Department of Medicinal Chemistry, Beijing Institute of Pharmacology and Toxicology, Beijing, China.
authors.forename: Zhongtang
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Pathophysiology, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Limei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Cong
authors.affiliation: Department of Pathophysiology, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Pathophysiology, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Pathophysiology, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Zuyin
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Microbiology, Fourth Military Medical University, 17 Changle Xi Road, Xi'an, Shaanxi Province, 710032, PR China.
authors.forename: Xingan
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Junxing
authors.initials: J
authors.lastname: Dong
authors.affiliation: Department of Medicinal Chemistry, Beijing Institute of Pharmacology and Toxicology, Beijing, China.
authors.forename: Rifang
authors.initials: R
authors.lastname: Yang
authors.affiliation: Department of Pathophysiology, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Yuwen
authors.initials: Y
authors.lastname: Cong
mesh_terms: D000179:Acrylates / Q000494:pharmacology*; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015237:Dinoprost / Q000037:antagonists & inhibitors*; D051379:Mice; D059226:Nociceptive Pain; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D014590:Uterine Contraction / Q000187:drug effects*
chemical_list: D000179:Acrylates; D000700:Analgesics; D000893:Anti-Inflammatory Agents; D011743:Pyrimidines; D015237:Dinoprost; C551593:fluacrypyrim