A mechanism of D‐(+)‐sotalol effects on heart rate not related to beta‐ adrenoceptor antagonism.

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Abstract
1. In order to determine whether the effects of d- or (+)-sotalol on heart rate are mediated by beta-adrenoceptor antagonism or might be due to other actions, we administered (+)-sotalol (400 mg every 12 h), atenolol (50 mg every 12 h) and placebo to eight healthy volunteers in a randomized, double-blind, crossover study. We also studied the affinity of human lymphocyte beta 2-adrenoceptor for (+)-sotalol, (-)- sotalol, and (+/−)-propranolol. 2. Compared with placebo, atenolol significantly reduced resting, standing and peak exercise heart rate whereas (+)-sotalol significantly reduced standing and peak exercise heart rate, but not resting heart rate. Atenolol significantly reduced resting, standing and peak exercise blood pressure while (+)-sotalol had no effect. 3. (+)-sotalol and atenolol both shifted the relationship between isoprenaline dose and heart rate to the right by similar degrees at the dosages tested. 4. (+)-sotalol but not atenolol significantly prolonged QTc interval. The degree of QTc prolongation due to (+)-sotalol, which has been shown to parallel action potential prolongation in the sinus node, correlated significantly with the reduction in peak exercise. heart rate it produced (r = 0.71, n = 8, P less than 0.05). 5. The affinity of the human lymphocyte beta 2- adrenoceptor was approximately 60-fold greater for (-)-sotalol (Ki, 108 +/− 12 nM) than for (+)-sotalol (Ki, 6,410 +/− 1,020 nM), and approximately 20,000-fold greater for (+/−)-propranolol (Ki, 0.33 +/− 0.08 nM) than for (+)-sotalol.(ABSTRACT TRUNCATED AT 250 WORDS)

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