RT Journal Article SR Electronic T1 Kinetic Interactions of Dopamine and Dobutamine with Human Catechol-O-methyltransferase and Monoamine Oxidase in Vitro JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 315 OP 321 DO 10.1124/jpet.301.1.315 VO 301 IS 1 A1 Maohe Yan A1 Leslie T. Webster, Jr. A1 Jeffrey L. Blumer YR 2002 UL http://jpet.aspetjournals.org/content/301/1/315.abstract AB Dopamine and dobutamine are often infused together into acutely ill patients requiring temporary support of cardiac and renal function, but whether these catecholamines affect the metabolic clearance of each other is not established. We determined the kinetics of dopamine and dobutamine as substrates and inhibitors of each other, i.e., apparentVmax, Km, andKi, with crude preparations of human blood mononuclear cell catechol-O-methyltransferase (COMT) and platelet monoamine oxidase (MAO) at pH 7.4 and 37°C. Values of Vmax for dopamine and dobutamine as substrates for COMT were 0.45 and 0.59 nmol of 3-O-methyl product formed per milligram of protein per minute, whereas those for Km were 0.44 and 0.05 mM, respectively. Dopamine and dobutamine were competitive inhibitors of each other in this reaction. TheKi for dopamine as an inhibitor of dobutamine methylation was 1.5 mM, whereas that for dobutamine as an inhibitor of dopamine methylation was 0.015 mM. Dopamine but not dobutamine was a substrate for MAO. TheVmax for dihydroxyphenylacetaldehyde formation from dopamine was 0.29 nmol/mg protein/min and theKm for dopamine was 0.38 mM. Dobutamine was a noncompetitive inhibitor of dopamine oxidation in this reaction (Ki ≅ 1.19 mM). The high apparent Km andKi values derived for dopamine and dobutamine when tested with these two human enzymes in vitro suggest that these catecholamines do not interfere with the metabolism of each other when both are infused together at therapeutic concentrations. The American Society for Pharmacology and Experimental Therapeutics