کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8533632 | 1560466 | 2016 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
In vivo analysis of torsadogenic potential of an antipsychotic drug paliperidone using the acute atrioventricular block rabbit as a proarrhythmia model
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
داروشناسی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
We assessed electrophysiological effects of an atypical antipsychotic drug paliperidone in acute atrioventricular block rabbits. Intravenous administration of paliperidone at a clinically relevant dose (0.06Â mg/kg) hardly affected the QT interval or monophasic action potential (MAP) duration, and the higher doses (0.6 and 6Â mg/kg) prolonged the QT interval and MAP duration. Meanwhile, premature ventricular contractions with R on T phenomenon were observed in 3 out of 6 animals at the middle dose, and torsades de pointes (TdP) episodes were detected in 2 out of 6 animals at the high dose. Intravenous administration of its chemically related compound risperidone at a clinically relevant dose (0.03Â mg/kg) hardly affected the electrophysiological parameters, and the higher doses (0.3 and 3Â mg/kg) prolonged the QT interval and MAP duration. Meanwhile, the premature ventricular contractions with R on T were observed in 2 out of 6 animals at the middle dose, and TdP episodes were detected in 4 out of 6 animals at the high dose. These results suggest that paliperidone showed torsadogenic potential at supra-therapeutic doses, whose potency can be estimated to be equal or slightly subordinate in comparison with that of risperidone.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmacological Sciences - Volume 132, Issue 1, September 2016, Pages 48-54
Journal: Journal of Pharmacological Sciences - Volume 132, Issue 1, September 2016, Pages 48-54
نویسندگان
Mihoko Hagiwara, Ryuichi Kambayashi, Megumi Aimoto, Yoshinobu Nagasawa, Akira Takahara,