Woosley R L, Barbey J T, Wang T, Funck-Brentano C
Department of Pharmacology, Georgetown University School of Medicine, Washington, D.C. 20007.
Am J Cardiol. 1990 Jan 2;65(2):22A-27A; discussion 35A-36A. doi: 10.1016/0002-9149(90)90197-9.
Sotalol, one of the first beta-receptor antagonists synthesized, is a promising investigational agent with remarkable efficacy for treatment of patients with ventricular and supraventricular arrhythmias. Unlike other beta blockers, sotalol also possesses class III antiarrhythmic action, evidenced by prolongation of the myocardial action potential duration. This additional action probably accounts for the greater antiarrhythmic efficacy of sotalol compared with other beta blockers. Sotalol's class III antiarrhythmic action becomes apparent at concentrations higher than those necessary for significant beta-receptor antagonism, both in vitro and in human subjects. In a study correlating dosage and antiarrhythmic response with prolongation of rate-corrected QT (QTc) (a measure of class III action) and the degree of beta-receptor blockade (assessed by the reduction of the maximal exercise-induced heart rate), 11 of 17 patients had an antiarrhythmic response. Eight of these 11 responders had been unresponsive to conventional beta-receptor antagonists. The plasma concentration associated with significant QTc prolongation (2.55 micrograms/ml) was found to be much greater than that associated with 50% reduction in maximal slowing of heart rate (0.8 micrograms/ml). As with other beta-receptor antagonists, the activities of sotalol's 2 stereoisomers differ, with the I-isomer having far more beta-blocking activity. However, both isomers have equal class III antiarrhythmic activity. When increasing doses of the d-isomer of sotalol (50 to 400 mg every 12 hours) were evaluated in patients with chronic ventricular arrhythmias, arrhythmia frequency was suppressed greater than 80% in 3 patients and 50% in 1 patient.(ABSTRACT TRUNCATED AT 250 WORDS)
索他洛尔是最早合成的β受体拮抗剂之一，是一种很有前景的研究药物，对治疗室性和室上性心律失常患者具有显著疗效。与其他β受体阻滞剂不同，索他洛尔还具有Ⅲ类抗心律失常作用，心肌动作电位时程延长证明了这一点。这种额外的作用可能是索他洛尔比其他β受体阻滞剂具有更高抗心律失常疗效的原因。索他洛尔的Ⅲ类抗心律失常作用在体外和人体中，在高于产生显著β受体拮抗作用所需的浓度时变得明显。在一项将剂量和抗心律失常反应与校正心率的QT（QTc，Ⅲ类作用的一种测量指标）延长以及β受体阻滞程度（通过最大运动诱发心率降低来评估）相关联的研究中，17名患者中有11名有抗心律失常反应。这11名有反应者中有8名对传统β受体拮抗剂无反应。发现与显著QTc延长相关的血浆浓度（2.55微克/毫升）远高于与最大心率减慢50%相关的血浆浓度（0.8微克/毫升）。与其他β受体阻滞剂一样，索他洛尔的两种立体异构体活性不同，I型异构体的β阻滞活性要强得多。然而，两种异构体具有相等的Ⅲ类抗心律失常活性。当对慢性室性心律失常患者评估递增剂量的索他洛尔d型异构体（每12小时50至400毫克）时，3名患者的心律失常频率抑制超过80%，1名患者抑制50%。（摘要截短于250字）
