Biomol Ther.  2015 Jul;23(4):386-389. 10.4062/biomolther.2015.033.

Cardiovascular Safety Pharmacology of Sibutramine

• Yun J
• Chung E
• Choi KH
• Cho DH
• Song YJ
• Han KM
• Cha HJ
• Shin JS
• Seong WK
• Kim YH
• Kim HS

• KMID: 2382370
• DOI: http://doi.org/10.4062/biomolther.2015.033

Abstract

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 IC50 of 3.92 muM in patch clamp assay and increased the heart rate and blood pressure (76 Deltabpm in heart rate and 51 DeltammHg in blood pressure) in beagle dogs at a dose of 30 mg/kg (per oral), while it shortened action potential duration (at 10 muM and 30 muM, resulted in 15% and 29% decreases in APD50, and 9% and 17% decreases in APD90, 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.

Keyword

Anorectic; Sibutramine; QT prolongation; Beagle dogs

MeSH Terms

Action Potentials
Animals
Blood Pressure
Cardiovascular System
Counterfeit Drugs
Dogs
Heart Rate
HEK293 Cells
Inhibitory Concentration 50
Pharmaceutical Preparations
Pharmacology*
Purkinje Fibers
Rabbits
Telemetry
Counterfeit Drugs
Pharmaceutical Preparations