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Paradoxical effect of sibutramine on autonomic cardiovascular regulation

Official URL:https://doi.org/10.1161/01.CIR.0000036370.31856.73
PubMed:View item in PubMed
Creators Name:Birkenfeld, A.L. and Schroeder, C. and Boschmann, M. and Tank, J. and Franke, G. and Luft, F.C. and Biaggioni, I. and Sharma, A.M. and Jordan, J.
Journal Title:Circulation
Journal Abbreviation:Circulation
Volume:106
Number:19
Page Range:2459-2465
Date:5 November 2002
Keywords:Obesity, Norepinephrine, Sympathetic Nervous System, Catecholamines
Abstract:Background- Sibutramine, a serotonin and norepinephrine transporter blocker, is widely used as an adjunctive obesity treatment. Norepinephrine reuptake inhibition with sibutramine conceivably could exacerbate arterial hypertension and promote cardiovascular disease. Methods and Results- In 11 healthy subjects (7 men, age 27±2 years, body mass index 23.1±0.7 kg/m2), we compared the effect of sibutramine or matching placebo (ingested 26, 14, and 2 hours before testing) on cardiovascular responses to autonomic reflex tests and to a graded head-up tilt test. In addition, we tested sibutramine in combination with metoprolol. Testing was conducted in a double-blind and crossover fashion. Supine systolic blood pressure was 113±3 mm Hg with placebo, 121±3 mm Hg with sibutramine (P<0.001 versus placebo), and 111±2 mm Hg with the combination of sibutramine and metoprolol. Similarly, sibutramine increased upright blood pressure. Sibutramine substantially increased upright heart rate. This effect was abolished with metoprolol. The blood pressure response to cold pressor and handgrip testing was attenuated with sibutramine compared with placebo. Furthermore, sibutramine decreased low-frequency oscillations of blood pressure and plasma norepinephrine concentrations in the supine position. Conclusions- The cardiovascular effect of the antiobesity drug sibutramine results from a complex interaction of peripheral and central nervous system effects. The inhibitory clonidine-like action of sibutramine on the central nervous system attenuates the peripheral stimulatory effect. Our findings strongly suggest that current concepts regarding the action of sibutramine on the sympathetic nervous system should be reconsidered.
ISSN:0009-7322
Publisher:American Heart Association (U.S.A.)
Item Type:Article

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