OBJECTIVE: To examine the effects of KUR-1246 on oxytocin-induced uterine contractions, the cardiovascular system, and general metabolism of pregnant sheep and their fetuses. METHODS: At 123-125 days' gestation, ewes (n = 8) were infused with oxytocin (1.0 mU/kg/minute) to induce uterine contractions. One hour later, KUR-1246 was infused for 3 consecutive hours beginning at a dose of 0.001 μg/kg/minute for 30 minutes and increasing stepwise every 30 minutes to 0.3 μg/kg/minute in the KUR-1246 group (n = 4). The control received saline instead (n = 4). Statistical comparisons of changes with time in the physiologic parameters between the two groups were carried out (analysis of variance). RESULTS: KUR-1246 suppressed oxytocin-induced uterine contractions more than 90% at doses over 0.03 μg/kg/minute. Significant differences between the two groups were found at high doses over 0.03 μg/kg/minute for the following parameters: maternal heart rate, diastolic blood pressure, mean blood pressure, base excess, blood K+, blood lactate, plasma glucose, plasma insulin, plasma nonesterified fatty acid levels, and fetal plasma glucose and plasma insulin levels. CONCLUSION: KUR-1246 significantly inhibited oxytocin-induced uterine contractions at doses over 0.03 μg/kg/minute and showed reduced cardiovascular and metabolic side effects compared with ritodrine hydrochloride studied earlier in pregnant sheep.
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