Cardioselectivity of prenalterol and isoproterenol

We examined the hemodynamic effects and kinetics of prenalterol, a new β‐adrenoceptor agonist, in 10 normal subjects. There is some doubt whether prenelterol is selective for β 1 adrenoceptors in animals; therefore, we also compared its cardioselectivity with that of the nonselective agonist, isoproterenol, with respect to heart rate (HR) and blood pressure (BP) responses after inhibition of cardiovascular reflexes with atropine, clonidine, and phentolamine. After intravenous (2.5 mg) and oral (10 mg and 100 mg) dosing, t½β was 2 to 3 hr. Oral bioavailability averaged 33% and was independent of dose. Oral prenalterol, 10 mg and 100 mg, increased resting HR, systolic BP, and cardiac index by up to 27% but had no significant effects during graded exercise. Prenalterol infusions were calculated to attain steady‐state plasma concentrations of 10, 20, and 40 ng/ml. HR and BP effects of the levels (10.8, 23.6, and 47.4 ng/ml) were compared with those of 0.5, 1.5, and 2.5 μg isoproterenol. Before autonomie block, prenalterol increased HR by 10 bpm at the highest dose and mean arterial pressure (MAP) by 10 mm Hg. In contrast, HR rose and MAP fell after isoproterenol. After block, at the highest doses of prenalterol and isoproterenol, there was an average rise in HR of 42 and 27 bpm; BP was almost maintained after the former but fell by 33 mm Hg after the latter. Prenalterol is an inotropic drug that has the effects of a full cardioselective β‐adrenoceptor agonist. Its inotropic effects are evident at doses that have little effect on HR because of the modifying effect of cardiovascular reflexes. The hemodynamic effects are most obvious at rest when sympathetic tone is low. Clinical Pharmacology and Therapeutics (1983) 34 , 749–757; doi: 10.1038/clpt.1983.245