Cirillo Rocco, Tos Enrico Gillio, Page Patrick, Missotten Marc, Quattropani Anna, Scheer Alexander, Schwarz Matthias K, Chollet André
Istituto di Ricerche Biomediche A. Marxer. Merck Serono, Colleretto Giacosa, Italy.
Am J Obstet Gynecol. 2007 Jul;197(1):54.e1-9. doi: 10.1016/j.ajog.2007.02.010.
The purpose of this study was to assess the tocolytic effect of AS604872, an orally active, potent, and selective prostanoid prostaglandin F2alpha receptor (FP) antagonist.
Compound AS604872 was characterized and tested for its ability to block uterine contraction and delay preterm parturition in rodent models.
AS604872 inhibited spontaneous uterine contractions in pregnant rat near term. In pregnant mouse, AS604872 delayed parturition induced by either the antiprogesterone RU-486 or the endotoxin lipopolysaccharide. Pups from treated mothers were delivered alive. The efficacy of AS604872 was superior to the beta-mimetic drug ritodrine. Combination of AS604872 and ritodrine showed an additive inhibitory effect on spontaneous uterine contractions in rat.
A selective antagonist of the FP receptor suppresses uterine contractility and delays labor. Our findings identify a new potential modality for the pharmacological management of preterm labor.
本研究旨在评估AS604872（一种口服活性、强效且选择性的前列腺素F2α受体（FP）拮抗剂）的保胎作用。
对化合物AS604872进行特性分析，并在啮齿动物模型中测试其阻断子宫收缩和延迟早产的能力。
AS604872抑制了近足月妊娠大鼠的自发性子宫收缩。在妊娠小鼠中，AS604872延迟了由抗孕激素RU-486或内毒素脂多糖诱导的分娩。经治疗的母鼠所产幼崽存活。AS604872的疗效优于β-拟交感神经药物利托君。AS604872与利托君联合使用对大鼠自发性子宫收缩显示出相加抑制作用。
FP受体的选择性拮抗剂可抑制子宫收缩力并延迟分娩。我们的研究结果确定了一种用于早产药物治疗的新潜在方法。
