Influence of sibutramine treatment on sympathetic vasomotor tone in obese subjects
ABSTRACT 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.
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.
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]).
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.
Article: Pharmacotherapy of obesity[Show abstract] [Hide abstract]
ABSTRACT: Obesity has become a significant health problem in industrialised and developing countries, and despite all nutritional and behavioural approaches, its prevalence is still increasing. In recent years, the identification and characterisation of central and peripheral mechanisms involved in the regulation of energy balance has made remarkable progress and provided numerous targets for novel anti-obesity agents. However, only few anti-obesity drugs are on the market and not many compounds have entered clinical development. In the present review, the clinically available agents are discussed and their pharmacological profiles are compared. Some of the drugs that are currently in clinical development are mentioned as examples of the possible future range of anti-obesity agents. Selected topics in drug discovery are presented to illustrate novel targets and concepts for the pharmacotherapy of obesity.Experimental and Clinical Endocrinology & Diabetes 11/2006; 114(9):475-84. DOI:10.1055/s-2006-924241 · 1.76 Impact Factor
Article: Sibutramine for obesity in adolescentsGARCIA-MORALES LM, BERBER A, MARCIA-LARA CC et al.: Use of sibutramine in obese Mexican adolescents: a 6-month randomized, double-blind, placebo-controlled, parallel group trial. Clin. Ther. (2006) 28:770-782 and BERKOWITZ RI, FUJIOKA K, DANIELS SR et al.: Effect of sibutramine treatment in obese adolescents: a randomized trial. Ann. Intern. Med. (2006) 145:81-90.[Show abstract] [Hide abstract]
ABSTRACT: In adolescents, there is an epidemic of being overweight or obese. Sibutramine has been shown to cause sustained loss of weight in adults. In a study based in Mexico City, adolescents with a BMI of 35/36 kg/m2, who were put on a hypocaloric diet and undertook physical activity, lost 4.3 kg in 6 months, and this loss was increased to 7.3 kg by sibutramine. Similarly, in a study based in the US, there was a loss of 1.9 kg in the placebo group of obese adolescents with a hypocaloric diet and increased physical activity at the end of 12 months, and this was increased to 6.5 kg in the sibutramine group. Sibutramine has a slight tendency to increase blood pressure and heart rate, and seems to be more effective than orlistat in causing weight loss in adolescents. However, orlistat does not have negative effects on blood pressure. Long-term follow-up studies of sibutramine in adolescents are needed to determine whether the weight loss is maintained, and whether the weight loss translates into better clinical outcomes.Expert Opinion on Pharmacotherapy 11/2006; 7(17). DOI:10.1517/146565188.8.131.525 · 3.09 Impact Factor