Pharmacokinetic and Pharmacodynamic Studies of Chlorpromazine in Rats : Effect of Chlorpromazine on Dopamine and Dopamine Metabolite Concentration in Rat Striatum
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概要
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The concentrations of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in rat striatum were increased after the i. v. administration of chlorpromazine (CPZ). Assuming that the enhancement of dopamine concentration in the striatum after CPZ administration is caused by the release of dopamine from the dopamine neuronal terminals, the relationship between the enhancement of dopamine concentration in the striatum and CPZ concentration in the cerebrospinal fluid (CSF) and the striatum were analyzed using the sigmoid E_<max> model. The enhancement of dopamine concentration in the striatum could be described quantitatively by this model. The time courses of DOPAC and HVA concentration in the striatum after CPZ administration were analyzed using the dopamine metabolism model, which has an apparent first-order clearance from dopamine to DOPAC and HVA, and also using the Michaelis-Menten type elimination kinetics of DOPAC and HVA. The values of the metabolism parameters for DOPAC and HVA were fixed to the estimated values of the L-dopa study. The calculated values of DOPAC and HVA concentrations in the striatum were greater than those of the observed data. The elimination parameters for DOPAC and HVA were reestimated by the nonlinear least squares method. The time courses of DOPAC and HVA concentration in the striatum could be described using these reestimated elimination parameters. These results indicated that the turnover rate of dopamine and dopamine metabolites, DOPAC and HVA in the striatum after CPZ administration is different from that after L-dopa administration. Thus, analysis using the dopamine metabolism model is a useful method not only for the quantitative explanation of the relationship between the CPZ concentration and the enlargement of dopamine concentration in the striatum, but also for the examination of the effect of CPZ on the turnover rate of dopamine and dopamine metabolites, DOPAC and HVA in the striatum.
- 社団法人日本薬学会の論文
- 1995-07-15
著者
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佐藤 眞治
新潟薬科大学薬剤学教室
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佐藤 真治
新潟薬科大学 薬理
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神代 昭
Department Of Pharmaceutics Niigata College Of Pharmacy
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佐藤 眞治
新潟薬科大学
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佐藤 眞治
Department of Pharmaceutics, Niigata College of Pharmacy
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小板橋 敏信
Department of Pharmaceutics, Niigata College of Pharmacy
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Koshiro Akira
Department Of Pharmaceutics Niigata College Of Pharmacy
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Koitabashi T
Department Of Biopharmaceutics Faculty Of Pharmaceutical Sciences Chiba University
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佐藤 眞治
Pharmaceutical Research Laboratories Ajinomoto Co. Inc.
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小板橋 敏信
Department Of Biopharmaceutics Faculty Of Pharmaceutical Sciences Chiba University
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小板橋 敏信
Department Of Pharmaceutics Niigata College Of Pharmacy
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