Electrophysiological safety of sibutramine HCl.
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 mug/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 microg/mL), L-type Ca current (IC50:2.709 +/- 0.4701 microg/mL), and Na current (IC50:7.718 +/- 1.7368 microg/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.
Kim
K S
KS
Department of pharmacology and National Research Laboratory, Korea Institute of Toxicology, Korea Research Institute of Chemical Technology, Yuseong, Daejeon, Korea. ejkim@kitox.re.kr
Park
S J
SJ
Lee
H A
HA
Kim
D K
DK
Kim
E J
EJ
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D001067:Appetite Depressants / Q000633:toxicity*; D003503:Cyclobutanes / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D051638:Ether-A-Go-Go Potassium Channels / Q000187:drug effects / Q000502:physiology; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D049990:Membrane Transport Modulators / Q000633:toxicity*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D010210:Papillary Muscles / Q000187:drug effects / Q000503:physiopathology
D001067:Appetite Depressants; D003503:Cyclobutanes; D051638:Ether-A-Go-Go Potassium Channels; D049990:Membrane Transport Modulators; C058254:sibutramine