Investigations with beta-adrenoceptor blocking drugs in healthy Volunteers

SummaryInvestigations of several properties of beta-adrenoceptor blocking drugs in healthy volunteers using simple non-invasive techniques giving reproducible results are described. A comparison of heart rate during physical exercise, before and after drug administration, showed that in this test 5 mg pindolol and 100 mg propranolol were almost equally active. In a test comparing the dose of intravenously infused isoprenaline required to increase the heart rate to 120 beatsjmin, pindolol was shown to be about 40-times more potent than propranolol and about 10-times less potent than Sandoz 23-784.The moderate intrinsic sympathomimetic activity (ISA) of pindolol leads to a slight increase in resting heart rate in subjects in the supine position when sympathetic tone is very low. In the sitting position pindolol, like propranolol (without ISA), reduces resting heart rate, but to a lesser extent. Sandoz 23-784, a drug with high ISA, however, increases resting heart rate both in the supine and in the sitting position.For comparative studies on the duration of action of different drugs, exercise-induced tachycardia seems most convenient. Experiments have shown that in equipotent doses pindolol (5 mg) exhibited a longer duration of action than propranolol (100 mg). Studies on the beta-adrenoceptor blocking activity of pindolol after oral and after i.v. administration support the results of pharmacokinetic studies showing a nearly complete absorption and a small first-pass effect for this drug in man.