Effects of Cisapride and Protective Effects of Mexiletine on the QTInterval in Rats
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概要
- 論文の詳細を見る
This study examined the effects of cisapride, a 5-HT_4 receptor agonist, on the QT interval in rats, and evaluated whether mexiletine, a potent antiarrhythmic drug, could prevent a cisapride-induced prolongation of the QT interval. The effects of drugs on electrocardiograms in anesthetized normal Lewis and heart failure rats were evaluated. The effects of cisapride were investigated by administering three different dosages (8,16 and 24mg/kg) for the acute study and one dosage (24mg/kg/day) for the chronic study (for 7 days) in control and ailing rats. After the oral administration of mexiletine at 30mg/kg for 1 week, cisapride at 24mg/kg was administered to the rats with heart failure (n=15 in each). After chronic cisapride treatment for 7 days, the QT intervals in control and ailing rats were prolonged from 68.0±1.6 (mean±s.e.m.) to 74.0±2.4msec and from 77.6±1.9 to 88.8±2.3 msec, respectively (p<0.05 and p<0.01). A single dosage of cisapride at 8 or 16 mg/kg did not affect the QT interval in control rats. However, with a single dose of cisapride at 8,16 and 24mg/kg in rats with heart failure, the QT interval increased dose-dependently from 75.5±1.9 to 81.2±1.8msec, 76.4±1.6 to 87.8±2.5msec, and 78.4±2.1 to 101.4±1.2msec, respectively (each, p<0.01). After the administration of mexiletine, cisapride had no such effects. Cisapride prolonged the QT interval in rats with heart failure dose-dependently, while mexiletine prevented the effect. These results indicate that a high dose of cisapride should be used carefully during illness, but mexiletine may prevent a cisapride-induced long QT interval.
- 新潟大学の論文
著者
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Aizawa Yoshiyasu
神戸大学 医学部
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Ma Meilei
Department Of Clinical Pharmacology Faculty Of Pharmaceutical Sciences Niigata University Of Pharmac
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Meilei Ma
Department Of Clinical Pharmacology Niigata College Of Pharmacy
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Watanabe Kenichi
Department Of Clinical Pharmacology Faculty Of Pharmaceutical Sciences Niigata University Of Pharmac
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Hirono S
Niigata Univ. Graduate School Of Medicine And Dental Sci. Niigata Jpn
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Kodama M
Niigata Univ. Graduate School Of Medicine And Dental Sci. Niigata Jpn
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Yoshimi Ohta
Department Of Clinical Pharmacology Niigata College Of Pharmacy
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Kenichi WATANABE
Department of Clinical Pharmacology, Niigata College of Pharmacy
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Ohta Yoshimi
Department Of Cardiology Saiseikai Kurihashi Hospital
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Watanabe K
Niigata Univ. Graduate School Of Medical And Dental Sci. Niigata Jpn
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Watanabe Koji
Division Of Hepatology And Gastroenterology Niigata University Graduate School Of Medical And Dental
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