Electrophysiological safety of sibutramine HCl

K. S. Kim; S. J. Park; H. A. Lee; D. K. Kim; E. J. Kim

doi:10.1177/0960327108095991

Electrophysiological safety of sibutramine HCl

K. S. Kim, S. J. Park, H. A. Lee, D. K. Kim, E. J. Kim

Department of Veterinary Medicine

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

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 (I_hERG), and inward currents (I_Na and I_Ca) 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: I_hERG (IC ₅₀:2.408 ± 0.5117 μg/mL), L-type Ca current (IC ₅₀:2.709 ± 0.4701 μg/mL), and Na current (IC ₅₀:7.718 ± 1.7368 μg/mL). Sibutramine blocked I _hERG, I_Ca, and I_Na 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 I _Ca and I_Na rather than I_hERG.

Original language	English
Pages (from-to)	553-558
Number of pages	6
Journal	Human and Experimental Toxicology
Volume	27
Issue number	7
DOIs	https://doi.org/10.1177/0960327108095991
State	Published - Jul 2008

Keywords

Action potential
L-type Ca channel
Na channel
Sibutramine HCl
hERG channel

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title = "Electrophysiological safety of sibutramine HCl",

abstract = "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 (IC 50:2.408 ± 0.5117 μg/mL), L-type Ca current (IC 50:2.709 ± 0.4701 μg/mL), and Na current (IC 50:7.718 ± 1.7368 μg/mL). Sibutramine blocked I hERG, 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 I Ca and INa rather than IhERG.",

keywords = "Action potential, L-type Ca channel, Na channel, Sibutramine HCl, hERG channel",

author = "Kim, {K. S.} and Park, {S. J.} and Lee, {H. A.} and Kim, {D. K.} and Kim, {E. J.}",

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AU - Park, S. J.

AU - Lee, H. A.

AU - Kim, D. K.

AU - Kim, E. J.

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AB - 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 (IC 50:2.408 ± 0.5117 μg/mL), L-type Ca current (IC 50:2.709 ± 0.4701 μg/mL), and Na current (IC 50:7.718 ± 1.7368 μg/mL). Sibutramine blocked I hERG, 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 I Ca and INa rather than IhERG.

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Electrophysiological safety of sibutramine HCl

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