Selectivity of antagonist and partial agonist activity of celiprolol in normal subjects

1. The aims of this study were to assess the relative beta 1/beta 2 selectivity of the antagonist and partial agonist activity (PAA) of celiprolol in man. 2. Eight normal males received single oral doses of celiprolol 200 mg (C200), 400 mg (C400) and 800 mg (C800); atenolol 50 mg (A50), 100 mg (A100) and 200 mg (A200); nadolol 40 mg (N40) and placebo (PL), administered in a single‐blind, randomised crossover design. 3. At rest, in the presence of low levels of circulating adrenaline and noradrenergic tone, a low dose of celiprolol (C200) showed evidence of beta 1‐PAA by significant increases in systolic blood pressure and resting heart rate. At higher doses (C400, C800), beta 2‐PAA became evident by a significant increase in postural finger tremor, whereas C200 had no effect. 4. In the presence of a beta 1‐ adrenoceptor agonist, as assessed by reduction of exercise tachycardia, increasing doses of celiprolol produced significantly less beta 1‐ adrenoceptor blockade compared with atenolol. Furthermore, there was no increase in beta 1‐adrenoceptor blockade beyond C400. 5. In the presence of a beta 2‐adrenoceptor agonist, as assessed by blunting of terbutaline‐induced chronotropic, hypokalaemic and finger tremor responses, celiprolol exhibited less beta 2‐adrenoceptor blockade than comparable doses of atenolol used in clinical practice. 6. Exercise hyperkalaemia was blunted significantly by C400 and C800 in comparison with all doses of atenolol and nadolol.