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Journal of the Society for Gynecologic Investigation, Vol. 11, No. 6, 384-387 (2004)
DOI: 10.1016/j.jsgi.2004.02.008

Inhibitory Effect of Barusiban and Atosiban on Oxytocin-Induced Contractions of Myometrium From Preterm and Term Pregnant Women

Piotr Pierzynski, MD, PhD

Adam Lemancewicz, MD, PhD

Torsten Reinheimer, MSc, PhD

Department of Pathophysiology of Pregnancy, Medical University of Bilystok, Bialystok, Poland; Ferring Pharmaceuticals A/S, International Center, Department of Non-Clinical Development, Copenhagen, Denmark; Department of Obstetrics and Gynaecology, University Hospital of Lund, Lund, Sweden

Mats Akerlund, MD, PhD

Department of Obstetrics and Gynaecology, University Hospital, S-221 85 Lund, Sweden mats.akerlund{at}gyn.lu.se

Tadeusz Laudanski, MD, PhD

Department of Pathophysiology of Pregnancy, Medical University of Bilystok, Bialystok, Poland; Ferring Pharmaceuticals A/S, International Center, Department of Non-Clinical Development, Copenhagen, Denmark; Department of Obstetrics and Gynaecology, University Hospital of Lund, Lund, Sweden

Background: A synthetic oxytocin analogue, barusiban, was shown to potently inhibit oxytocininduced activity of myometrium from term pregnant women. The responsiveness to vasopressin was not influenced by the compound.

Objective: To test the effect of barusiban and a reference compound, atosiban, on oxytocin-induced activity of myometrium from women at preterm pregnancy in comparison to myometrium from women at term.

Methods: Fifteen preterm (30-36 gestational weeks) and 12 term pregnant women (38-41 weeks) who underwent cesarean delivery donated myometrial tissue for the study. Concentration-response curves following oxytocin administration to isolated myometrial stips were recorded in control experiments, in the presence of barusiban at concentrations of 2.5, 25, and 250 nM, and of atosiban at concentrations of 25, 250, and 750 nM. Effective concentration 50% (EC50) and pA2 values were calculated.

Results: Both antagonists in higher concentrations increased the EC50 values to oxytocin. The median pA2 value for preterm myometrium with barusiban was 9.76 and with atosiban 7.86. For term myometrium the corresponding pA2 results were 9.89 and 7.81, respectively. None of these pA2 values differed to any statistically significant degree.

Conclusion: The selective oxytocin antagonist, barusiban, concentration-dependently inhibits oxytocin-induced myometrial contractions of both preterm and term myometrium at least as potently as atosiban. It remains to be determined if the selectivity of barusiban for the oxytocin receptor confers an advantage over atosiban as a tocolytic in preterm labor.

Key Words: Oxytocin • receptor antagonist • human myometrial activity • pA2 value • barusiban • atosiban


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