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

Sep 8, 2004Journal of the Society for Gynecologic Investigation

Barusiban and atosiban reduce oxytocin-triggered uterine contractions in early and late pregnancy

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Abstract

The median pA2 value for preterm myometrium with barusiban was 9.76, compared to 7.86 with atosiban.

Both barusiban and atosiban increased the effective concentration 50% (EC50) values to oxytocin at higher concentrations.
For term myometrium, the median pA2 values were 9.89 for barusiban and 7.81 for atosiban.
No statistically significant differences were observed between the pA2 values for preterm and term myometrium with either antagonist.
Barusiban concentration-dependently inhibits oxytocin-induced contractions in both preterm and term myometrium.

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BACKGROUND: A synthetic oxytocin analogue, barusiban, was shown to potently inhibit oxytocin-induced 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 strips 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.

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

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