Cardiac dose-response relationships of oral and intravenous pindolol.

The dose-response curve of pindolol on exercise heart rate has been constructed from observations in healthy male subjects studied 2 h after oral doses of pindolol 0.25 mg, 0.5 mg, 1 mg, 2.5 mg, 5 mg, 10 mg and 20 mg. This dose-response curve has been compared with historical controls who received atenolol, oxprenolol, practolol, propranolol and sotalol. The dose-response curves differ in the relative potency of the drug, the maximum reduction of heart rate and possibly in the slope of the curves. Pindolol is extremely potent. At doses which produce 15% reduction of exercise heart rate, the relative potencies of the drugs were: pindolol (1), atenolol (1:21) oxprenolol (1:19), practolol (1:44), propranolol (1:25) and sotalolol (1:160). The maximum effects produced by pindolol, oxprenolol and practolol were less than those of the other β-adrenoceptor blocking drugs, an effect which is probably the result of their partial agonist activity. Following intravenous pindolol 0.005, 0.01, 0.02 and 0.045 mg/kg the reduction of exercise heart rate and duration of action were dose-dependent. The effects of pindolol 0.045 mg/kg i.v. (mean total dose 3.5 mg), pindolol 5 mg p.o., propranolol 0.3 mg/kg i.v. (mean total dose 25.1 mg) and propranolol 80 mg p.o. were assessed on resting, standing and exercise heart rates. Neither drug reduced resting heart rate but propranolol reduced standing heart rate from 98.8 to 80.3 beats/min. The effects of all four preparations on exercise heart rate were similar. Oral pindolol is approximately 16-20 times as potent as oral propranolol. Intravenous pindolol is approximately 6-8 times as potent as intravenous propranolol.