KUR-1246, a novel beta(2)-adrenoceptor agonist, as a tocolytic agent

Obstet Gynecol. 2002 Sep;100(3):487-94. doi: 10.1016/s0029-7844(02)02141-5.

Abstract

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 microg/kg/minute for 30 minutes and increasing stepwise every 30 minutes to 0.3 microg/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 microg/kg/minute. Significant differences between the two groups were found at high doses over 0.03 microg/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 microg/kg/minute and showed reduced cardiovascular and metabolic side effects compared with ritodrine hydrochloride studied earlier in pregnant sheep.

Publication types

  • Comparative Study

MeSH terms

  • Acetamides / pharmacology*
  • Adrenergic beta-Agonists / pharmacology*
  • Animals
  • Blood Glucose / analysis
  • Blood Glucose / drug effects
  • Blood Pressure Determination
  • Female
  • Fetal Monitoring
  • Gestational Age
  • Heart Rate / drug effects
  • Hemodynamics / physiology
  • Models, Animal
  • Naphthalenes / pharmacology*
  • Obstetric Labor, Premature / prevention & control*
  • Oxytocin
  • Pregnancy
  • Pregnancy Outcome*
  • Pregnancy, Animal
  • Probability
  • Ritodrine / pharmacology*
  • Sensitivity and Specificity
  • Sheep
  • Tocolytic Agents / pharmacology*
  • Uterine Contraction / drug effects*

Substances

  • Acetamides
  • Adrenergic beta-Agonists
  • Blood Glucose
  • Naphthalenes
  • Tocolytic Agents
  • bedoradrine
  • Oxytocin
  • Ritodrine