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1 Department of Pharmacology, University of Göteborg, Göteborg, Sweden
In rabbit cerebral cortex slices, dopamine was deaminated to the two phenolic acids, 3,4-dihydroxyphenylacetic acid and homovanillic acid, whereas norepinephrine was deaminated primarily to the two phenolic glycols, 3-methoxy-4-hydroxyphenylglycol and 3,4-dihydroxyphenylglycol. Only negligible amounts of 3-methoxy-4-hydroxyphenylethanol and 3,4-dihydroxyphenylethanol could be detected after incubation with dopamine. No normetanephrine could be detected from newly formed norepinephrine but considerable quantities of normetanephrine were isolated from exogenously added norepinephrine. This observation was taken as support for the view that newly formed norepinephrine is initially catabolized by intraneuronal monoamine oxidase and subsequently by extraneuronal catechol-O-methyltransferase, whereas exogenously added norepinephrine can be catabolized initially by either enzyme. Pretreatment of rabbits with the monoamine oxidase inhibitor nialamide reduced the deaminated catabolites of both norepinephrine and dopamine to negligible quantities. Nialamide pretreatment also produced a 6-fold increase in methoxytyramine after incubation with dopamine and a 1.5-fold increase in normetanephrine after incubation with norepinephrine. Increasing doses of nialamide increased the net synthesis of norepinephrine. The total synthesis of norepinephrine (norepinephrine plus catabolites) was also increased with the largest dose of nialamide employed, 100 mg/kg.
Submitted on March 6, 1967
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