Inotropic selectivity of dobutamine enantiomers in the pithed rat.
The inotropic selectivities of the (-)- and (+)-enantiomers of dobutamine were assessed in pithed rat by comparing the relative ability of each enantiomer to increase left ventricular contractility (left ventricular dp/dt) and heart rate. The (-)-enantiomer of dobutamine, which is predominantly an alpha-1 adrenoceptor agonist, displayed greater inotropic selectivity than the (+)-enantiomer, which is predominantly a beta-1 and beta-2 adrenoceptor agonist. Pretreatment with the alpha-1 adrenoceptor antagonist prazosin significantly inhibited the effect of (-)-dobutamine on left ventricular dp/dt, but did not affect the chronotropic activity of this enantiomer. As such, pretreatment with prazosin decreased the inotropic selectivity of (-)-dobutamine. In contrast, the inotropic activity and selectivity of (+)-dobutamine were not affected by prazosin pretreatment. These results indicate that the inotropic effects of (-)-dobutamine are mediated, at least in part, by alpha-1 adrenoceptors. We conclude, based on the marked inotropic activity of (-)-dobutamine and the greater inotropic selectivity of (-)-dobutamine over (+)-dobutamine, that alpha-1 adrenoceptors may play a role in the inotropic activity and selectivity of racemic dobutamine used clinically. The possible involvement of both myocardial alpha-1 and beta-1 adrenoceptors in the inotropic activity of dobutamine must be considered.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003655:Decerebrate State; D004280:Dobutamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism; D013268:Stimulation, Chemical
D004280:Dobutamine; D011224:Prazosin