Effect of MCI-186 on ischemia-induced changes in monoamine metabolism in rat brain.
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.
Oishi
R
R
Department of Pharmacology, Okayama University Medical School, Japan.
Itoh
Y
Y
Nishibori
M
M
Watanabe
T
T
Nishi
H
H
Saeki
K
K
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D000983:Antipyrine / Q000494:pharmacology; D015306:Biogenic Monoamines / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001929:Brain Edema / Q000139:chemically induced / Q000209:etiology / Q000378:metabolism; D002545:Brain Ischemia / Q000139:chemically induced / Q000150:complications / Q000378:metabolism*; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D000077553:Edaravone; D006719:Homovanillic Acid / Q000378:metabolism; D007700:Kinetics; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D011145:Polyvinyls; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism; D013687:Telencephalon / Q000187:drug effects / Q000378:metabolism
D015306:Biogenic Monoamines; D011145:Polyvinyls; D015102:3,4-Dihydroxyphenylacetic Acid; C013215:polyvinyl acetate; D012701:Serotonin; D000077553:Edaravone; D000983:Antipyrine; D004298:Dopamine; D009638:Norepinephrine; D006719:Homovanillic Acid