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 (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 (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 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.

Keywords

action potential hERG channel L-type Ca channel Na channel sibutramine HCl

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