Comparison of bisoprolol with other beta-adrenoceptor blocking drugs.

beta 1-Selectivity or beta 1/beta 2-splitting, i.e., the selectivity ratio between the potency of a beta-blocking agent to block beta 1-versus beta 2-mediated responses, was assessed in 16 healthy male volunteers. The study was carried out to an intraindividual, randomized crossover design comparing bisoprolol (0.07 mg/kg i.v.) with the following beta-blocking agents: acebutolol (0.8 mg/kg i.v.), metoprolol (0.2 mg/kg i.v.), penbutolol (0.04 mg/kg i.v.), and propranolol (0.2 mg/kg i.v.). Exercise tachycardia was used as a mainly beta 1-receptor-mediated response: the beta-blocking effect was quantified as a work load ratio after/before beta-blockade for a given heart rate. Decrease in diastolic blood pressure after isoprenaline was used as a mainly beta 2-receptor-mediated response: the beta-blocking effect was quantified as an isoprenaline dose ratio after/before beta-blockade for a decrease in diastolic blood pressure of 25 mm Hg. Assessing the data for a beta 1/beta 2-splitting as 1 for propranolol, the relative beta 1-selectivity (mean +/- SEM) was 12.2 +/- 1.1 for bisoprolol, 9.0 +/- 0.9 for metoprolol, 6.2 +/- 0.6 for acebutolol, and 0.6 +/- 0.06 for penbutolol. There was a significant difference (p less than 0.01) between the cardioselective compounds bisoprolol, metoprolol, and acebutolol on one side, and the nonselective compounds propranolol and penbutolol on the other side. Within the group of nonselective compounds, propranolol and penbutolol differed from each other (p less than 0.05), penbutolol being even less beta 1-selective than propranolol. Within the group of "cardioselective" compounds, bisoprolol and metoprolol appeared to be superior to acebutolol (p less than 0.05). However, it cannot be dismissed that these within-group differences merely reflect the considerable decrease of plasma levels of acebutolol and penbutolol which were observed after ergometric exercise in comparison with the plasma levels after isoprenaline tests.