Document Detail


Paradoxical effect of sibutramine on autonomic cardiovascular regulation.
MedLine Citation:
PMID:  12417543     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Andreas L Birkenfeld; Christoph Schroeder; Michael Boschmann; Jens Tank; Gabi Franke; Friedrich C Luft; Italo Biaggioni; Arya M Sharma; Jens Jordan
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Publication Detail:
Type:  Clinical Trial; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Circulation     Volume:  106     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2002 Nov 
Date Detail:
Created Date:  2002-11-05     Completed Date:  2002-11-12     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2459-65     Citation Subset:  AIM; IM; S    
Affiliation:
Franz-Volhard Clinical Research Center, Medical Faculty of the Charité, Humboldt-University, Berlin, Germany.
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MeSH Terms
Descriptor/Qualifier:
Adrenergic beta-Antagonists / therapeutic use
Adult
Anti-Obesity Agents / pharmacology
Autonomic Nervous System / drug effects*
Baroreflex / drug effects
Biological Clocks / drug effects,  physiology
Blood Pressure / drug effects
Cardiovascular Physiological Phenomena / drug effects*
Cardiovascular System / drug effects*,  innervation*
Cold Temperature
Cross-Over Studies
Cyclobutanes / pharmacology*
Double-Blind Method
Female
Hand Strength
Heart Rate / drug effects
Humans
Male
Metoprolol / pharmacology
Norepinephrine Plasma Membrane Transport Proteins
Physical Stimulation / methods
Reference Values
Symporters / drug effects,  metabolism
Tilt-Table Test
Valsalva Maneuver / physiology
Chemical
Reg. No./Substance:
0/Adrenergic beta-Antagonists; 0/Anti-Obesity Agents; 0/Cyclobutanes; 0/Norepinephrine Plasma Membrane Transport Proteins; 0/SLC6A2 protein, human; 0/Symporters; 106650-56-0/sibutramine; 37350-58-6/Metoprolol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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