Arrest of preterm labor in rat and mouse by an oral and selective nonprostanoid antagonist of the prostaglandin F2alpha receptor (FP)

  • Am J Obstet Gynecol. 2007 Jul;197(1):54.e1-9. doi: 10.1016/j.ajog.2007.02.010.
Rocco Cirillo  1 ,  Enrico Gillio Tos ,  Patrick Page ,  Marc Missotten ,  Anna Quattropani ,  Alexander Scheer ,  Matthias K Schwarz ,  André Chollet
Affiliations
  • 1. Istituto di Ricerche Biomediche A. Marxer. Merck Serono, Colleretto Giacosa, Italy.
PMID: 17618756 DOI: 10.1016/j.ajog.2007.02.010
Abstract

Objective: 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.

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.

Products