Delay of preterm birth in sheep by THG113.31, a prostaglandin F2α receptor antagonist

Objective: A novel prostaglandin F-2 alpha receptor antagonist, THG113.31, was tested for the suppression of uterine contractility and delay of preterm labor in sheep. Study design: We determined the tocolytic effectiveness of THG113.31 on contractions that were stimulated in vitro by prostaglandin F-2 alpha and E-2 in longitudinal and circular myometrial strips. We also tested the ability of THG113.31 in vivo to lower uterine electromyographic activity that was induced by the progesterone receptor blocker, RU486, and to delay preterm birth. Results: THG113.31 suppressed the amplitude of prostaglandin F-2 alpha, but not prostaglandin E-2-induced contractions of both circular and longitudinal myometrium (P <.01). The times to delivery after RU486 were 34.8 +/- 1.1 hours (saline solution) and 41.9 +/- 0.5 hours (THG113.31; P <.001) or an average delay of 7.1 hours. There were no changes in fetal blood gases (Pao(2), Paco(2), pH, or Sao(2)) because of THG113.31. Fetal cortisol levels rose in each group, and fetal and maternal prostaglandin E-2 and F-2 alpha, metabolite concentrations rose similarly in both groups. Conclusion: THG113.31 specifically suppresses prostaglandin F-2 alpha-induced myometrial contractility and delays delivery. (c) 2005 Elsevier Inc. All rights reserved.