Karita M, Sato H, Koretsune Y, Imai K, Ozaki H, Yokoyama H, Hori M, Takeda H, Inoue M, Kamada T
First Department of Medicine, Osaka University School of Medicine, Japan.
Eur J Clin Pharmacol. 1995;48(6):467-71. doi: 10.1007/BF00194336.
The effects of a combination regimen of metoprolol and beta 1-adrenoceptor agonist denopamine on resting and exercise heart rate have been studied in 10 normal volunteers. Maximal ramp upright bicycle exercise was performed three times at 1-week intervals. Two hours before each exercise test, 5 mg metoprolol plus 20 mg denopamine, 5 mg metoprolol plus a denopamine placebo, or two placebos were orally administered in a double-blind fashion. During exercise after placebo administration, heart rate increased in parallel with the exercise intensity. Compared to the placebo values, resting heart rate was significantly decreased by an average of 10 beats.min-1 by 5 mg metoprolol, whereas it was not altered by the combination regimen. During exercise, however, both the combination regimen and metoprolol alone showed a significant negative chronotropic effect, decreasing peak exercise heart rate by an average of 14 and 21 beats.min-1, respectively. Peak oxygen uptake was also significantly decreased by both regimens. We conclude that concomitant administration of 5 mg metoprolol and 20 mg denopamine exerts an effective beta-adrenoceptor blocking action during exercise but a minimal effect at rest in normal subjects. The combination regimen appears to have a favourable pharmacological profile for beta-adrenoceptor blocker therapy in patients with chronic heart failure.
在10名正常志愿者中研究了美托洛尔与β1 -肾上腺素能受体激动剂多巴胺丁胺联合用药方案对静息心率和运动心率的影响。以1周的间隔进行3次最大斜坡直立自行车运动。在每次运动测试前2小时，以双盲方式口服5毫克美托洛尔加20毫克多巴胺丁胺、5毫克美托洛尔加多巴胺丁胺安慰剂或两种安慰剂。服用安慰剂后运动期间，心率随运动强度平行增加。与安慰剂值相比，5毫克美托洛尔使静息心率平均显著降低10次/分钟，而联合用药方案未使其改变。然而，在运动期间，联合用药方案和美托洛尔单独使用均显示出显著的负性变时作用，分别使运动峰值心率平均降低14次/分钟和21次/分钟。两种用药方案也均使峰值摄氧量显著降低。我们得出结论，在正常受试者中，同时给予5毫克美托洛尔和20毫克多巴胺丁胺在运动期间发挥有效的β -肾上腺素能受体阻断作用，但在静息时作用最小。该联合用药方案似乎对慢性心力衰竭患者的β -肾上腺素能受体阻滞剂治疗具有良好的药理学特征。
