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Stroke, Vol 20, 1557-1564, Copyright © 1989 by American Heart Association

ARTICLES

Effect of MCI-186 on ischemia-induced changes in monoamine metabolism in rat brain

R Oishi, Y Itoh, M Nishibori, T Watanabe, H Nishi and K Saeki
Department of Pharmacology, Okayama University Medical School, Japan.

We examined the effects of MCI-186 (3-methyl-1-phenyl-2-pyrazolin-5- one), a novel free radical scavenger and an inhibitor of ischemia- induced brain edema, on monoamine metabolism in the brains of both normal and ischemic rats. In normal rats, 3 mg/kg i.v. MCI-186, a dose that prevents ischemic brain edema, had no significant effect on brain concentrations of dopamine, norepinephrine, 5-hydroxytryptamine, or their metabolites. After the injection of 5 microliters of 3% polyvinyl acetate into the left internal carotid artery, concentrations of 3,4- dihydroxyphenylacetic acid and homovanillic acid markedly increased, but that of norepinephrine decreased, in the left telencephalon of embolized rats compared with control rats injected with vehicle; the concentration of 5-hydroxyindoleacetic acid also increased slightly. These effects were maximal 2 hours after embolization. The turnover rate of dopamine between 6 and 8 hours after embolization was significantly higher but that of norepinephrine was slightly lower than that in vehicle-treated rats. When rats were treated with 3 mg/kg i.v. MCI-186 immediately after the injection of polyvinyl acetate, the embolization-induced changes in monoamine metabolism were less marked. Our results suggest that MCI-186 attenuates ischemia-induced changes in brain monoamine metabolism, probably due to its free radical scavenging action, although it has no marked effect in normal rats.

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