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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Cardioselectivity of prenalterol and isoproterenol.

We examined the hemodynamic effects and kinetics of prenalterol, a new beta-adrenoceptor agonist, in 10 normal subjects. There is some doubt whether prenalterol is selective for beta 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, t 1/2 beta 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 micrograms isoproterenol. Before autonomic 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 beta-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.[1]

References

  1. Cardioselectivity of prenalterol and isoproterenol. Jennings, G., Bobik, A., Oddie, C., Hargreaves, M., Korner, P. Clin. Pharmacol. Ther. (1983) [Pubmed]
 
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