The metabolism of C14-norepinephrine in the central nervous system



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The purpose of this study was to develop methodology for the accurate determination of the metabolites of C14-norepinephrine in the central nervous system of the rat and to study the effects of various drugs on the distribution pattern of these metabolites. For these studies, the labeled norepinephrine was administered directly into the brains of the rats by an intraventricular injection. These animals were either treated with ethanol or disulfiram or were controls. The brains were removed, homogenized and centrifuged. The supernatants were diluted and divided into three equal portions for an unhydrolyzed aliquot and hydrolysis with Glusulase or [beta]-glucuronidase. The samples were assayed for C14-norepinephrine and its metabolites using ion exchange resins, aluminum oxide columns, and ethyl acetate extraction. The per cent of the total radioactivity as norepinephrine and as each metabolite was determined. It was found in these studies that some of the metabolites of norepinephrine occur as sulfate or glucuronide conjugates in the central nervous system. 3,4-Dihydroxyphenylglycol-O-sulfate was found as a new metabolite of norepinephrine in the rat brain. The existence of this metabolite in the sulfate conjugate form was verified using thin layer chromatography. Although the distribution of the metabolites of norepinephrine was unaffected by the administration of ethanol, disulfiram caused a significant increase in 3,4-dihydroxyphenylglycol and decrease in 3-methoxy-4-bydroxymandelic acid.