HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Kiguchi, S. Articles by Fujimoto, S. Search for Related Content PubMed PubMed Citation Articles by Kiguchi, S. Articles by Fujimoto, S.

KUR-1246, a Novel ß₂-Adrenoceptor Agonist, as a Tocolytic Agent

From the Pharmacology Research Laboratory, Research and Development, Kissei Pharmaceutical Co. Ltd., Matsumoto City, Japan; and the Departments of Obstetrics and Gynecology and Pediatrics, Hokkaido University School of Medicine, Sapporo, Japan.

Address reprint requests to: Tadashi Matsuda, MD, Hokkaido University School of Medicine, Department of Obstetrics and Gynecology, North 15, West 7, Kitaku, Sapporo 060-8638, Japan; E-mail: choku{at}med.hokudai.ac.jp.

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 non-esterified 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.