D-SOTALOL REDUCES HEART-RATE INVIVO THROUGH A BETA-ADRENERGIC-RECEPTOR INDEPENDENT MECHANISM

被引:14
作者
YASUDA, SU
BARBEY, JT
FUNCKBRENTANO, C
WELLSTEIN, A
WOOSLEY, RL
机构
[1] ST ANTOINE UNIV HOSP,CLIN PHARMACOL UNIT,PARIS,FRANCE
[2] GEORGETOWN UNIV,MED CTR,DEPT MED,WASHINGTON,DC 20007
关键词
D O I
10.1038/clpt.1993.48
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
d-Sotalol was developed as an antiarrhythmic agent with a relative lack of antagonist activity at beta-adrenergic receptors. Exercise heart rate reduction has been observed after administration to humans. The purpose of this study was to determine directly whether this effect of d-sotalol was attributable to beta-blockade. Plasma samples from normal volunteers who randomly received either atenolol, d-sotalol, or placebo were used in an in vitro radioreceptor assay to determine occupancy of beta1-adrenergic receptors by antagonist present in the plasma. Occupancy was compared with the observed pharmacologic effects. A reduction in exercise heart rate of 7.7% +/- 3.8% for d-sotalol and 15.9% +/- 3.0% for atenolol occurred with beta1-adrenergic receptor occupancy of 0% and 33.9% +/- 21.4%, respectively. Absence of antagonist effect in the radioreceptor assay eliminates the potential role of beta1-blockade in d-sotalol-induced heart rate reduction. This effect is most likely a result of prolongation of the sinus node action potential duration.
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页码:436 / 442
页数:7
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