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Cardiovascular Safety Pharmacology of Sibutramine
- Source :
- Biomolecules & Therapeutics
- Publication Year :
- 2015
- Publisher :
- The Korean Society of Applied Pharmacology, 2015.
-
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 μM in patch clamp assay and increased the heart rate and blood pressure (76 Δbpm in heart rate and 51 ΔmmHg in blood pressure) in beagle dogs at a dose of 30 mg/kg (per oral), while it shortened action potential duration (at 10 μM and 30 μM, 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.
- Subjects :
- Drug
media_common.quotation_subject
hERG
QT prolongation
Pharmacology
Biochemistry
QT interval
Drug Discovery
Heart rate
medicine
Sibutramine
Adverse effect
media_common
biology
business.industry
Blood pressure
Beagle dogs
biology.protein
Anorectic
Molecular Medicine
Original Article
business
medicine.drug
Subjects
Details
- ISSN :
- 19769148 and 20054483
- Volume :
- 23
- Database :
- OpenAIRE
- Journal :
- Biomolecules & Therapeutics
- Accession number :
- edsair.doi.dedup.....9c772c9c8c168536a245fde1a9bbebda