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

Objective A novel prostaglandin F2α 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 F2α and E2 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 F2α, but not prostaglandin E2–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 (Pao2, Paco2, pH, or Sao2) because of THG113.31. Fetal cortisol levels rose in each group, and fetal and maternal prostaglandin E2 and F2α metabolite concentrations rose similarly in both groups. Conclusion THG113.31 specifically suppresses prostaglandin F2α–induced myometrial contractility and delays delivery.