Effect of diphenylhydantoin on the uptake and catabolism of l-[3H]norepinephrine in vitro in rat cerebral cortex tissue |
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Authors: | Albert J Azzaro JoséA Gutrecht David J Smith |
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Institution: | 1. Neuropharmacology Research Laboratory, Department of Neurology, West VirginiaU.S.A.;2. University Medical Center, Morgantown, W. Va. 26506, U.S.A. |
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Abstract: | The effect of diphenylhydantoin on the accumulation of 3H]norepinephrine in vitro was examined in brain slices prepared from rat cerebral cortex. High concentrations of diphenylhydantoin (10?3 M) caused a significant reduction in the 5-min accumulation of 3H]norepinephrine. On the other hand, 10?5–10?4 M diphenylhydantoin facilitated the 20-min accumulation of 3H]norepinephrine. This facilitative action of diphenylhydantoin was (1) associated with a reduction in oxidative catabolism of 3H]norepinephrine and (2) abolished by the 2-hr pretreatment of rats with 100 mg/kg of nialamide (i.p.). The inhibitory action of diphenylhydantoin on the oxidative catabolism of 3H]norepinephrine was observed in both whole and lyzed crude synaptosomal preparations. When diphenylhydantoin and pargyline were compared, it was found that pargyline was 37 times more effective than diphenylhydantoin in inhibiting the oxidative deamination of 3H]norepinephrine. These results suggest that diphenylhydantoin alters norepinephrine metabolism in cerebral cortex slices by an inhibitory action on (1) monoamine oxidase activity and (2) the neuronal uptake system. |
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