Yasuda S U, Barbey J T, Funck-Brentano C, Wellstein A, Woosley R L
Department of Pharmacology, Georgetown University Medical Center, Washington, DC 20007.
Clin Pharmacol Ther. 1993 Apr;53(4):436-42. doi: 10.1038/clpt.1993.48.
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 beta 1-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 beta 1-adrenergic receptor occupancy of 0% and 33.9% +/- 21.4%, respectively. Absence of antagonist effect in the radioreceptor assay eliminates the potential role of beta 1-blockade in d-sotalol-induced heart rate reduction. This effect is most likely a result of prolongation of the sinus node action potential duration.
d - 索他洛尔作为一种抗心律失常药物被研发出来，其在β - 肾上腺素能受体处相对缺乏拮抗活性。在给予人类用药后，已观察到运动心率降低的情况。本研究的目的是直接确定d - 索他洛尔的这种效应是否归因于β - 受体阻滞作用。从随机接受阿替洛尔、d - 索他洛尔或安慰剂的正常志愿者采集的血浆样本，用于体外放射受体测定，以确定血浆中存在的拮抗剂对β1 - 肾上腺素能受体的占有率。将占有率与观察到的药理效应进行比较。d - 索他洛尔使运动心率降低7.7%±3.8%，阿替洛尔使运动心率降低15.9%±3.0%，此时β1 - 肾上腺素能受体占有率分别为0%和33.9%±21.4%。放射受体测定中缺乏拮抗剂效应，排除了β1 - 受体阻滞在d - 索他洛尔引起的心率降低中所起的潜在作用。这种效应很可能是窦房结动作电位时程延长的结果。
