THE EFFECTS OF LOWER THAN CONVENTIONAL DOSES OF ORAL NADOLOL ON RELATIVE BETA(1) BETA(2)-ADRENOCEPTOR BLOCKADE/

1 The aim of the present study was to evaluate the relative beta(1)/be ta(2) antagonist selectivity of the beta-adrenoceptor blocker nadolol, in lower than conventional clinical doses. 2 Eight normal volunteers received single oral doses of either placebo (PL), nadolol 5 mg (N5), 20 mg (N20) or 80 mg (N80) in a single-blind, randomised crossover des ign. beta(1)-adrenoceptor antagonism was assessed by attenuation of ex ercise tachycardia, and beta(2)-adrenoceptor blockade by effects on sa lbutamol-induced chronotropic, hypokalaemic and finger tremor response s. The relative percentage attenuation of beta(2) and beta(1)-mediated responses was calculated and expressed as beta(2):beta(1) selectivity ratios. 3 Nadolol produced dose-related reductions in exercise tachyc ardia in keeping with increasing beta(1)-adrenoceptor blockade; mean % reduction (95% CI) compared with placebo: N5 10.7 (6.6 to 14.8), N20 21.4 (17.3 to 25.4), N80 38.9 (34.8 to 42.9). However, even the lowest dose of nadolol (5 mg) produced almost complete blunting of beta(2)-m ediated effects and significantly increased exercise hyperkalaemia; pe ak exercise hyperkalaemia (mmol l(-1)) (means and 95% CI): PL 4.88 (4. 68 to 5.07), N5 5.36 (5.17 to 5.55), N20 5.48 (5.28 to 5.67), N80 5.42 (5.22 to 5.61). beta(2):beta(1) selectivity ratios significantly incr eased as the dose of nadolol was reduced. 4 These data suggest that wh ereas in the clinical dose range nadolol behaves as a non-selective be ta-adrenoceptor antagonist, as the dose is reduced this drug demonstra tes an increasing degree of selectivity for the beta(2)-adrenoceptor. 5 Low-dose oral nadolol may therefore be a useful selective beta(2)-ad renoceptor antagonist for research studies in man.