Birkenfeld Andreas L, Schroeder Christoph, Boschmann Michael, Tank Jens, Franke Gabi, Luft Friedrich C, Biaggioni Italo, Sharma Arya M, Jordan Jens
Franz-Volhard Clinical Research Center, Medical Faculty of the Charité, Humboldt-University, Berlin, Germany.
Circulation. 2002 Nov 5;106(19):2459-65. doi: 10.1161/01.cir.0000036370.31856.73.
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.
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.
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.
西布曲明是一种血清素和去甲肾上腺素转运体阻滞剂，被广泛用作肥胖症的辅助治疗药物。西布曲明抑制去甲肾上腺素再摄取，理论上可能会加剧动脉高血压并促进心血管疾病。
在11名健康受试者（7名男性，年龄27±2岁，体重指数23.1±0.7kg/m²）中，我们比较了西布曲明或匹配的安慰剂（在测试前26、14和2小时服用）对自主反射测试和分级头高位倾斜试验的心血管反应的影响。此外，我们测试了西布曲明与美托洛尔联合使用的效果。测试以双盲交叉方式进行。安慰剂组仰卧位收缩压为113±3mmHg，西布曲明组为121±3mmHg（与安慰剂相比，P<0.001），西布曲明与美托洛尔联合使用组为111±2mmHg。同样，西布曲明使直立位血压升高。西布曲明显著增加直立位心率。美托洛尔可消除这种作用。与安慰剂相比，西布曲明使冷加压和握力测试的血压反应减弱。此外，西布曲明降低了仰卧位血压的低频振荡和血浆去甲肾上腺素浓度。
抗肥胖药物西布曲明的心血管效应源于外周和中枢神经系统效应的复杂相互作用。西布曲明对中枢神经系统的抑制性可乐定样作用减弱了外周刺激作用。我们的研究结果强烈表明，关于西布曲明对交感神经系统作用的当前概念应重新考虑。
