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


CONCLUSIONS
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.
Kiguchi
Sumiyoshi
S
Pharmacology Research Laboratory, Research and Development, Kissei Pharmaceutical Co. Ltd., Matsumoto City, Japan.
Matsuda
Tadashi
T
Cho
Kazutoshi
K
Okuyama
Kazuhiko
K
Akahane
Masuo
M
Fujimoto
Seiichiro
S
D000081:Acetamides / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects; D001795:Blood Pressure Determination; D005260:Female; D005323:Fetal Monitoring; D005865:Gestational Age; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000502:physiology; D023421:Models, Animal; D009281:Naphthalenes / Q000494:pharmacology*; D007752:Obstetric Labor, Premature / Q000517:prevention & control*; D010121:Oxytocin; D011247:Pregnancy; D011256:Pregnancy Outcome; D011270:Pregnancy, Animal; D011336:Probability; D012312:Ritodrine / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D012756:Sheep; D015149:Tocolytic Agents / Q000494:pharmacology*; D014590:Uterine Contraction / Q000187:drug effects*
D000081:Acetamides; D000318:Adrenergic beta-Agonists; D001786:Blood Glucose; D009281:Naphthalenes; D015149:Tocolytic Agents; C425888:bedoradrine; D010121:Oxytocin; D012312:Ritodrine