THE METABOLISM OF EPINEPHRINE CONTAINING ISOTOPIC CARBON IN MAN

Schizophrenic patients of both sexes and a normal male subject were given infusions of epinephrine labeled with carbon¹⁴ at the beta position or at the methyl group. Blood pressure and pulse were recorded at regular intervals during the infusion. Urine samples were collected at regular intervals prior to, and for at least thirty hours following infusion. Aliquots of each urine sample were extracted for epinephrine by the alumina adsorption method of von Euler and Hellner and bioassayed by the method of Gaddum and Lembeck; aliquots were also placed on duplicate planchets and counted in triplicate on a gas flow counter. The infusion and post-infusion urines were combined, lyophilized and extracted with a variety of organic solvents. Determinations of radioactivity, and paper chromatographic analyses were carried out on each extract.

The hemodynamic responses were found to be directly related to the rate of infusion of epinephrine, and were no longer apparent ten minutes after administration ceased. The infusion of epinephrine resulted in an increase in the urinary excretion of biologically active epinephrine which ranged from 1 to 5 per cent of the dose administered. In contrast to this, 91 ± 3 per cent of the radioactivity contained in the infused beta-labeled epinephrine and 34 ± 3 per cent of the radioactivity contained in the infused methyl-labeled epinephrine were excreted in the urine. The chromatograms of the chloroform, ether and butanol extracts of the lyophilized urine of subjects infused with beta-labeled epinephrine showed a major radioactive peak with an average Rf value of 0.77. Similar extracts of the lyophilized urine of patients infused with methyl-labeled epinephrine did not contain such radioactive peaks. The data are consistent with the hypothesis that in the metabolites of epinephrine the alpha and beta carbons are intact and attached to the benzene nucleus. In addition, approximately two thirds of the molecules of infused epinephrine lose their methyl groups during metabolism.