In Vivo Analysis of Adrenergic Receptor Activity of Dobutamine

Abstract

Studies were performed in anesthetized dogs to evaluate the cardiac and systemic effects of intravenously administered dobutamine and to determine its direct effects on the renal and femoral vascular beds. The results demonstrated that dobutamine possessed an inotropic efficacy similar to that of isoproterenol and norepinephrine; its chronotropic effect was similar to or greater than that of norepinephrine. In contrast to norepinephrine, dobutamine increased cardiac output and reduced total peripheral resistance with minimal effects on mean aortic pressure. Studies on the denervated hind limb demonstrated that dobutamine stimulated both alpha and beta receptors. The dose of dobutamine which produced a 50% increase in femoral blood flow was 180 times the required dose of isoproterenol and the dose which produced a 50% increase in contractile force was 43 times the required dose of isoproterenol. Studies on the renal vasculature demonstrated that dobutamine caused no dopaminelike renal vasodilator activity and only minor vasodilation mediated by beta receptors. We concluded that dobutamine is more cardioselective than is isoproterenol. The dobutamine-induced decrease in peripheral resistance observed in the whole dog was presumably due to increased myocardial contractility coupled with a greater net effect of beta-adrenergic vasodilation than alpha-adrenergic vasoconstriction. Studies with reserpine-treated dogs showed that all dobutamine-induced effects were due to a direct action on receptors.

Dopexamine: a novel agonist at peripheral dopamine receptors and β2‐adrenoceptors

“…Another N-alkylated dopamine analogue, dobutamine, developed as an inotropic agent (Tuttle & Mills, 1975) is inactive as an agonist at vascular DA,-receptors (Robie et al, 1974) and at prejunctional DA2-receptors of the rabbit ear artery (unpublished observations), but is active in stimulating al-, PI-and P2-adrenoceptors (Maccarone et al, 1984).…”

Cardiovascular Effects of a New Positive Inotropic Agent, (−)-(R)-1-(p-Hydroxyphenyl)-2-[(3,4-Dimethoxyphenethyl) Amino]-Ethanol (TA-064) in the Anesthetized Dog and Isolated Guinea Pig Heart

“…Tuttle and Mills (1) also reported that the mild effect of dobutamine on blood pressure is ascribed to a balance between alpha-and beta2-agonistic effects. It has been reported that the apparent inotropic selectivity of dobutamine in vivo is partly due to its peripheral vascular effect (12)(13)(14). In conscious instrumented dogs, TA-064 had a high inotropic selectivity (15, 16).…”

Effects of dobutamine and terbutaline on the secretion of glycoproteins from the acinar cells of the rat submandibular gland.

“…2A, Table 2A). This result may be attributed to a low level of activity toward 132-adrenoceptors of dobutamine, which was suggested by observations of the relaxation of vascular smooth muscle (25)(26)(27) and the adenylate cyclase or GTPase activity in ery throcyte membranes of the turkey and frog (28). Furthermore, pretreatment with me toprolol more strongly inhibited the secretion of fluid and protein induced by terbutaline than pretreatment with ICI-118551 (Fig.…”