Inotropic selectivity of dobutamine enantiomers in the pithed rat

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 235; no. 2; p. 344
• Main Authors: Ruffolo, Jr, R R, Messick, K
• Format: Journal Article
• Language: English
• Published: United States 01-01-1985
• Subjects: Animals; Blood Pressure - drug effects; Decerebrate State; Dobutamine - pharmacology; Dose-Response Relationship, Drug; Heart Rate - drug effects; Male; Myocardial Contraction - drug effects; Prazosin - pharmacology; Rats; Rats, Inbred Strains; Stereoisomerism; Stimulation, Chemical
• ISSN: 0022-3565

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.