Arrest of preterm labor in rat and mouse by an oral and selective nonprostanoid antagonist of the prostaglandin F2α receptor (FP)

被引：26
作者：
Cirillo, Rocco
Tos, Gillio
Page, Patrick
Missotten, Marc
Quattropani, Anna
Scheer, Alexander
Schwarz, Matthias K.
Chollet, Andre
机构：
[1] Merck Serono, CH-1202 Geneva, Switzerland
[2] Ist Ric Biomed A Marxer Merck Serono, Colleretto Giacosa, Italy
来源：
AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY | 2007年 / 197卷 / 01期
关键词：
myometrium contractility; preterm labor; prostaglandin F2 alpha receptor antagonist; prostaglandins; rat and mouse preterm parturition; tocolytics;
D O I：
10.1016/j.ajog.2007.02.010
中图分类号：
R71 [妇产科学];
学科分类号：
100211 ;
摘要：
OBJECTIVE: The purpose of this study was to assess the tocolytic effect of AS604872, an orally active, potent, and selective prostanoid prostaglandin F2 alpha receptor (FP) antagonist. STUDY DESIGN: Compound AS604872 was characterized and tested for its ability to block uterine contraction and delay preterm parturition in rodent models. RESULTS: 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. CONCLUSION: 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.
引用
收藏
页码：54.e1 / 54.e9
页数：9
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