The metabolic fate of H3-epinephrine and C14-metanephrine in the rat.

The major metabolites of epinephrine have been recently identified as the 0-methylated derivatives, 3-methoxy-4-hydroxymandelic acid (1)) metanephrine (2)) and 3-methoxy-4hydroxyphenylglycol (3). The corresponding catechols, 3,4dihydroxymandelic acid (4), 3,4-dihydroxyphenylglycol (5)) and epinephrine and its conjugates (6) were found to be minor excretion products. The present study was designed to determine the relative magnitudes of the various metabolic pathways (Fig. 1) for administered epinephrine in normal rats and in animals pretreated with agents which inhibit catechol-O-methyl transferase and monoamine oxidase, i.e. the enzymes involved in the metabolism of epinephrine. Catechol-O-methyl transferase was inhibited with pyrogallol (7) and monoamine oxidase with iproniazid (8). The recently described technique for the study of alternate metabolic pathways with simultaneous administration of epinephrine-7-H3 and metanephrine-methoxy-Cl4 (9) was used in this study.