Investigations with Beta‐Adrenoceptor Blocking Drugs in Healthy Volunteers

Several properties of beta‐adrenoceptor blocking drugs can be investigated in healthy volunteers with simple non‐invasive techniques giving reproducible results. Beta‐adrenoceptor blocking activity can be evaluated in several ways. One is to compare heart rate during physical exercise before and after drug administration. 5 mg pindolol and 100 mg propranolol were about equiactive in this test. Another method is to administer i.v. infusions of isoprenaline before and after the administration of the antagonist and to determine the dose of isoprenaline required to increase heart rate to 120 beats/min. Pindolol is about 40 times more potent than propranolol and Sandoz 23–784 about 10 times more potent than pindolol in this test. The moderate intrinsic sympathomimetic activity (ISA) of pindolol leads to a slight increase in resting heart rate of 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, 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) exhibits 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.