Article date: August 1990
By: C Funk‐Brentano, DJ Silberstein, DM Roden, AJ Wood, RL Woosley, in Volume 30, Issue 2, pages 195-202
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)
DOI: 10.1111/j.1365-2125.1990.tb03765.x
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