Pharmacodynamics and drug action
Clinical Pharmacology & Therapeutics (2006) 79, 500–508; doi: 10.1016/j.clpt.2006.02.002
Influence of sibutramine treatment on sympathetic vasomotor tone in obese subjects*
Karsten Heusser MD1,2, Jens Tank MD1,2, Andre Diedrich MD1,2, Stefan Engeli MD1,2, Susanne Klaua MD1,2, Nadine Krüger1,2, Anke Strauss RN1,2, Gritt Stoffels RN1,2, Friedrich C. Luft MD1,2 and Jens Jordan MD1,2
- 1Franz-Volhard Clinical Research Center, Medical Faculty of the Charité and HELIOS Klinkum, Berlin, Germany
- 2Autonomic Dysfunction Service, Vanderbilt University, Nashville, Tenn
Correspondence: Jens Jordan, MD, Franz-Volhard Clinical Research Center, Haus 129, Charité-Campus Buch, Wiltbergstrasse 50, 13125 Berlin, Germany E-mail: jordan@fvk.charite-buch.de
*This work was supported in part by research grants from Abbott Laboratories and by the Deutsche Forschungsgemeinschaft
Received 16 August 2005; Accepted 1 February 2006.
Abstract
Background: Sibutramine, a serotonin and norepinephrine transporter blocker, is used as adjunctive obesity treatment. Studies in healthy subjects suggested that sibutramine might have opposing effects on peripheral and central sympathetic activity; an increase in blood pressure has been claimed. Direct measurements of muscle sympathetic nerve activity (MSNA) in sibutramine-treated patients have not been conducted.
Methods and Results: Twenty nondiabetic obese men and women completed the study (mean body mass index, 35 
3 kg/m2; mean age, 42 8 years). They were treated for 5 days with 15 mg sibutramine per day or matching placebo in a randomized, double-blind, crossover fashion. At the end of each intervention, heart rate, blood pressure, and MSNA were recorded. Patients underwent cold pressor testing and phenylephrine and nitroprusside infusions.
Results: The mean blood pressure (systolic/diastolic) was 118 13 mm Hg/70 9 mm Hg with placebo and 120 13 mm Hg/69 8 mm Hg with sibutramine (P=.29). The mean resting MSNA was 28 14 bursts/min with placebo and 12 10 bursts/min with sibutramine (P < .0001). Sibutramine attenuated the rise in blood pressure (25 9 mm Hg/9 9 mm Hg versus 31 12 mm Hg/14 9 mm Hg, P < .01) and MSNA (0.3 0.5 arbitrary units/min versus 1.0 1.1 arbitrary units/min, P=.01) in response to cold pressor testing. Baroreflex heart rate control was similar with sibutramine and with placebo. The sympathetic baroreflex was shifted such that at a given blood pressure, MSNA was substantially decreased (top, 44 1.23 bursts/min versus 58 2.99 bursts/min [P < .001]; center point, 65 0.32 mm Hg versus 67 0.81 mm Hg [P < .05]).
Conclusions: Sibutramine treatment profoundly and selectively reduces sympathetic nerve traffic at rest and attenuates the responsiveness to sympathetic stimuli. Our data support the idea that sibutramine's peripheral sympathomimetic effect is counteracted by a central sympatholytic mechanism.
