Effect of Inhibiting both Catechol-O-Methyl Transferase and Monoamine Oxidase on Cardiovascular Responses to Norepinephrine

The simultaneous inhibition of catechol-O-methyl transferase and monoamine oxidase (by pyrogallol and JB-835) produced only moderate prolongation of the cardiovascular effects of injected l-norepinephrine in anesthetized dogs. This prolongation of pharmacological action in presence of enzyme inhibitors was correlated with a delayed disappearance of injected norepinephrine from the circulation. While these results indicate that metabolism by these enzymes contributes to removal of circulating norepinephrine from the plasma in the dog, they further suggest that the physiological inactivation of circulating norepinephrine at the receptor sites does not require metabolic destruction of the amine by these enzymes.