Effects of 5-HT(4) receptor agonists, cisapride and mosapride citrate on electrocardiogram in anaesthetized rats and guinea-pigs and conscious cats
| Autor: | Masafumi Yabuuchi, Isamu Nose, Tsugutaka Ito, Yasuyuki Mizuki, Katsuyoshi Nakatsuji, Yoshihide Kii |
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| Rok vydání: | 2001 |
| Předmět: |
Male
medicine.medical_specialty Consciousness medicine.drug_class Health Toxicology and Mutagenesis Heart Ventricles Morpholines Guinea Pigs Toxicology QT interval Rats Sprague-Dawley Electrocardiography Heart Rate Internal medicine Heart rate medicine Antiemetic Animals Anesthesia Pharmacology Cisapride CATS biology Dose-Response Relationship Drug business.industry Fissipedia biology.organism_classification Mosapride Rats Serotonin Receptor Agonists Dose–response relationship Long QT Syndrome Endocrinology Benzamides Cats Female business medicine.drug |
| Zdroj: | Pharmacologytoxicology. 89(2) |
| ISSN: | 0901-9928 |
| Popis: | The purpose of this study was to examine the arrhythmogenic potential of 5-HT4 receptor agonists, cisapride and mosapride citrate (mosapride) in vivo. In anaesthetized rats, cisapride at intravenous infusion of 10 and 30 mg/kg/hr for 1 hr prolonged the electrocardiographic RR and QT intervals, whereas at 3 mg/kg/hr, it prolonged the RR interval without affecting the QT interval. Mosapride at 30 mg/kg/hr for 1 hr slightly, but not significantly, prolonged the QT interval. In anaesthetized guinea-pigs, cisapride at intravenous infusion of 0.3, 1 and 3 mg/kg over 15 min. prolonged the RR interval (18-44%), QT interval (18-42%) and the corrected QT interval (QTc; 8-19%). Mosapride at 3, 10 and 30 mg/kg over 15 min. little affected the QTc although at 30 mg/kg, it slightly prolonged the RR and QT intervals. With repeated oral administrations of 30 mg/kg twice a day for 7 days, cisapride prolonged the QT interval (11-35%) and QTc (11-32%) at the 3rd and 7th days in conscious cats. In addition, cisapride depressed the ST segment in two out of five cats. Mosapride at 60 mg/kg twice a day for 7 days did not affect the QT interval or QTc in cats. The maximal plasma concentrations of mosapride and its main metabolite (a des-4-fluorobenzyl-mosapride) at the 7th day in cats were 9.4+/-2.8 microM and 2.5+/-0.3 microM , respectively, being 100 and 30-60 times higher than those in man given therapeutic doses (Sakashita et al. 1993a&b). These results indicate that mosapride has little arrhythmogenic potential. |
| Databáze: | OpenAIRE |
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