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Human & Experimental Toxicology
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research-article

Electrophysiological safety of sibutramine HCl

KS Kim

Department of pharmacology and National Research Laboratory, Korea Institute of Toxicology, Korea Research Institute of Chemical Technology, Yuseong, Daejeon, Korea ejkim{at}kitox.re.kr

SJ Park

Department of pharmacology and National Research Laboratory, Korea Institute of Toxicology, Korea Research Institute of Chemical Technology, Yuseong, Daejeon, Korea

HA Lee

Department of pharmacology and National Research Laboratory, Korea Institute of Toxicology, Korea Research Institute of Chemical Technology, Yuseong, Daejeon, Korea

DK Kim

Department of Physiology, Konyang University College of Medicine, Daejeon, Korea ejkim{at}kitox.re.kr

EJ Kim

Department of pharmacology and National Research Laboratory, Korea Institute of Toxicology, Korea Research Institute of Chemical Technology, Yuseong, Daejeon, Korea ejkim{at}kitox.re.kr

Sibutramine is known to induce cardiovascular side effects such as tachycardia, vasodilation, and hypertension. The present study was aimed to examine the effects of sibutramine on action potential of guinea pig papillary muscle, recombinant hERG currents (IhERG), and inward currents (INa and ICa) of rat ventricular myocytes. Sibutramine at 30 µg/mL induced a shortening of action potential duration (APD) of guinea pig papillary muscle; on average, APD30 and APD90 were shortened by 23% and 17% at a stimulation rate of 1 Hz, respectively. Sibutramine suppressed the following currents: IhERG (IC50:2.408 ± 0.5117 µg/mL), L-type Ca current (IC50:2.709 ± 0.4701 µg/mL), and Na current (IC50:7.718 ± 1.7368 µg/mL). Sibutramine blocked IhERG, ICa, and INa in a concentration-dependent manner. In conclusion, sibutramine exerted a shortening effect on APD in guinea pig papillary muscle through its more powerful blocking effects on ICa and INa rather than IhERG.

Key Words: action potential • hERG channel • L-type Ca channel • Na channel • sibutramine HCl

Human & Experimental Toxicology, Vol. 27, No. 7, 553-558 (2008)
DOI: 10.1177/0960327108095991
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