title: Paradoxical effect of sibutramine on autonomic cardiovascular regulation.
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.
  
  
  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.affiliation: Franz-Volhard Clinical Research Center, Medical Faculty of the Charité, Humboldt-University, Berlin, Germany.
authors.forename: Andreas L
authors.initials: AL
authors.lastname: Birkenfeld
authors.forename: Christoph
authors.initials: C
authors.lastname: Schroeder
authors.forename: Michael
authors.initials: M
authors.lastname: Boschmann
authors.forename: Jens
authors.initials: J
authors.lastname: Tank
authors.forename: Gabi
authors.initials: G
authors.lastname: Franke
authors.forename: Friedrich C
authors.initials: FC
authors.lastname: Luft
authors.forename: Italo
authors.initials: I
authors.lastname: Biaggioni
authors.forename: Arya M
authors.initials: AM
authors.lastname: Sharma
authors.forename: Jens
authors.initials: J
authors.lastname: Jordan
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000328:Adult; D019440:Anti-Obesity Agents / Q000494:pharmacology; D001341:Autonomic Nervous System / Q000187:drug effects*; D017704:Baroreflex / Q000187:drug effects; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects*; D002319:Cardiovascular System / Q000187:drug effects* / Q000294:innervation*; D003080:Cold Temperature; D018592:Cross-Over Studies; D003503:Cyclobutanes / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D018737:Hand Strength; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000494:pharmacology; D050484:Norepinephrine Plasma Membrane Transport Proteins; D010812:Physical Stimulation / Q000379:methods; D012016:Reference Values; D027981:Symporters / Q000187:drug effects / Q000378:metabolism; D018667:Tilt-Table Test; D014636:Valsalva Maneuver / Q000502:physiology
chemical_list: D000319:Adrenergic beta-Antagonists; D019440:Anti-Obesity Agents; D003503:Cyclobutanes; D050484:Norepinephrine Plasma Membrane Transport Proteins; C493227:SLC6A2 protein, human; D027981:Symporters; D008790:Metoprolol; C058254:sibutramine