Paradoxical effect of sibutramine on autonomic cardiovascular regulation.

Article Details

Citation

Copy to clipboard

Birkenfeld AL, Schroeder C, Boschmann M, Tank J, Franke G, Luft FC, Biaggioni I, Sharma AM, Jordan J

Paradoxical effect of sibutramine on autonomic cardiovascular regulation.

Circulation. 2002 Nov 5;106(19):2459-65.

PubMed ID

12417543 [ View in PubMed

]

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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Sibutramine	Sodium-dependent noradrenaline transporter	Protein	Humans	Yes	Inhibitor	Details
Sibutramine	Sodium-dependent serotonin transporter	Protein	Humans	Yes	Inhibitor	Details