The inhibition of both spontaneous and oxytocininduced contractions of human pregnant myometrium by the oxytocin receptor antagonist, OBE001

Abstract

Introduction Currently the only drug licensed in Europe for inhibition of preterm contractions is the intravenous oxytocin (OT)/arginine vasopressin receptor antagonist Atosiban. OBE001 is a more selective OT receptor antagonist than Atosiban and may be administered orally. Here we compare the effects of Atosiban and OBE001 on spontaneous and OT-induced contractions of human pregnant myometrium in vitro. Methods Experiments were performed using a DMT Myograph 800MS in oxygenated Kreb's solution, with ADI POWERLAB software allowing simultaneous measurements of eight muscle preparations. Once regular contractions had been established for 20+ min, baseline measurement of contraction frequency, contraction peak, contraction duration, work per contraction (average area under curve) and total work (area under all contractions) were made. Results Atosiban had no effect upon spontaneous concentrations but antagonised the effects of oxytocin upon the rate of contractions and peak tension with a dose-dependent effect, although at lowest concentrations the effects were partly agonistic. OBE001 was studied at equimolar concentrations. OBE001 inhibited spontaneous contractions as well as OT-induced contractions in a dose-dependent way, affecting rate, contraction peak tension and contraction duration and therefore having an overall effect upon total work done. At 600 nM concentration of OBE001, it resulted in a complete abolishment of contractility. Conclusion When comparing the effect of Atosiban and OBE001 at equimolar concentrations, OBE001 was superior to Atosiban at 60 nM and 600 nM, and unlike Atosiban, totally inhibited contractility. Therefore, OBE001 appears to be a promising candidate tocolytic with a better tocolytic profile than Atosiban.