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논문 기본 정보

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학술저널
저자정보
Yun, Jaesuk (National Institute of Drug and Safety Evaluation, Ministry of Food and Drug Safety) Chung, Eunyong (National Institute of Drug and Safety Evaluation, Ministry of Food and Drug Safety) Choi, Ki Hwan (National Institute of Drug and Safety Evaluation, Ministry of Food and Drug Safety) Cho, Dae Hyun (National Institute of Drug and Safety Evaluation, Ministry of Food and Drug Safety) Song, Yun Jeong (National Institute of Drug and Safety Evaluation, Ministry of Food and Drug Safety) Han, Kyoung Moon (National Institute of Drug and Safety Evaluation, Ministry of Food and Drug Safety) Cha, Hey Jin (National Institute of Drug and Safety Evaluation, Ministry of Food and Drug Safety) Shin, Ji Soon (National Institute of Drug and Safety Evaluation, Ministry of Food and Drug Safety) Seong, Won-Keun (National Institute of Drug and Safety Evaluation, Ministry of Food and Drug Safety) Kim, Young-Hoon (National Institute of Drug and Safety Evaluation, Ministry of Food and Drug Safety) Kim, Hyung Soo (National Institute of Drug and Safety Evaluation, Ministry of Food and Drug Safety)
저널정보
한국응용약물학회 Biomolecules & Therapeutics(구 응용약물학회지) Biomolecules & therapeutics 제23권 제4호
발행연도
2015.1
수록면
386 - 389 (4page)

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Sibutramine is an anorectic that has been banned since 2010 due to cardiovascular safety issues. However, counterfeit drugs or slimming products that include sibutramine are still available in the market. It has been reported that illegal sibutramine-contained pharmaceutical products induce cardiovascular crisis. However, the mechanism underlying sibutramine-induced cardiovascular adverse effect has not been fully evaluated yet. In this study, we performed cardiovascular safety pharmacology studies of sibutramine systemically using by hERG channel inhibition, action potential duration, and telemetry assays. Sibutramine inhibited hERG channel current of HEK293 cells with an $IC_{50}$ of $3.92{\mu}M$ in patch clamp assay and increased the heart rate and blood pressure ($76{\Delta}bpm$ in heart rate and $51{\Delta}mmHg$ in blood pressure) in beagle dogs at a dose of 30 mg/kg (per oral), while it shortened action potential duration (at $10{\mu}M$ and $30{\mu}M$, resulted in 15% and 29% decreases in $APD_{50}$, and 9% and 17% decreases in $APD_{90}$, respectively) in the Purkinje fibers of rabbits and had no effects on the QTc interval in beagle dogs. These results suggest that sibutramine has a considerable adverse effect on the cardiovascular system and may contribute to accurate drug safety regulation.
#Anorectic #Sibutramine #QT prolongation #Beagle dogs

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참고문헌 (10)

참고문헌 신청
Heal, D. J. / 1998 / Sibutramine: a novel anti-obesity drug. A review of the pharmacological evidence to differentiate it from damphetamine and d-fenfl uramine / Int. J. Obes. Relat. Metab. Disord 22:S18~S28 google schola 허승혜 / 2013 / A Case of Dilated Cardiomyopathy with Massive Left Ventricular Thrombus after Use of a Sibutramine-Containing Slimming Product / Korean Circulation Journal 43(9):632~635 dbpia James, W. P. / 2010 / Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects / N. Engl. J. Med 363:905~917 google schola Kim, E. J. / 2005 / Effects of combined treatment with sildenafi l and itraconazole on the cardiovascular system in telemetered conscious dogs / Drug Chem. Toxicol 28:177~186 google schola Kim, K. S. / 2008 / Electrophysiological safety of sibutramine HCl / Hum. Exp. Toxicol 27:553~558 google schola

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