Neurotoxic Convulsions Induced by Theophylline and Its Metabolites in Mice
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概要
- 論文の詳細を見る
To evaluate the risk of neurotoxicity induced by theophylline and its main metabolites, 1-methylxanthine (1-MX), 3-methylxanthine (3-MX), 1,3-dimethyluric acid (1,3-DMUA) and 1-methyluric acid (1-MUA), we compared their convulsive potency to central nervous system (CNS) after intracerebral administration to mice. All compounds studied induced clonic convulsion in a dose-dependent manner, and the ED_<50> values for convulsion were 490,546,1107,360 and 620 nmol/kg for theophylline, 1-MX, 3-MX, 1,3-DMUA and 1-MUA, respectively. These compounds were also administered intravenously to mice by constant rate infusion until the onset of convulsion. Clonic convulsion was induced by i.v. infusion of theophylline, 1-MX and 3-MX, while convulsion was not observed during 1,3-DMUA or 1-MUA infusion for 60 min. This finding may be due to the poor blood-brain barrier permeability of both 1-MUA and 1,3-DMUA as compared with theophylline, 1-MX and 3-MX. However, it may be also necessary to consider the possibility of 1,3-DMUA-induced-neurotoxicity judging from its intrinsic convulsive potency.
- 1996-06-15
著者
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KAWAKAMI Junichi
Department of Pharmacy, The University of Tokyo Hospital, Faculty of Medicine, University of Tokyo
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YAMAMOTO Koujirou
Department of Pharmacy, The University of Tokyo Hospital, Faculty of Medicine, University of Tokyo
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IGA Tatsuji
Department of Pharmacy, University of Tokyo Hospital, Faculty of Medicine, University of Tokyo
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Sawada Y
Department Of Pharmaceutics Graduate School Of Pharmacertical Sciences Kyushu University
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Sawada Yasufumi
Faculty Of Pharmaceutical Sciences Tokushima Bunri University:faculty Of Pharmaceutical Sciences Uni
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Yamamoto Koujirou
Department Of Pharmacy The University Of Tokyo Hospital Faculty Of Medicine The University Of Tokyo
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Yamamoto Koujirou
Department Of Pharmacy The Gunma University Hospital Gunma University School Of Medicine:department
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Yamamoto Koujirou
Department Of Clinical Pharmacology Gunma University School Of Medicine
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Yamamoto Koujirou
Department Of Clinical Pharmacology Gunma University Graduate School Of Medicine
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Iga T
Department Of Pharmacy University Of Tokyo Hospital
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Iga Tatsuji
Department Of Biopharmaceutics Faculty Of Pharmaceutical Sciences Nagoya City University:department
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Kawakami Junichi
Department Of Hospital Pharmacy Hamamatsu University School Of Medicine
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Kawakami Junichi
Dep. Of Hospital Pharmacy Hamamatsu Univ. School Of Medicine
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TOYAMA Etsuko
Department of Pharmacy, The University of Tokyo Hospital, Faculty of Medicine, The University of Tok
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Toyama Etsuko
Department Of Pharmacy The University Of Tokyo Hospital Faculty Of Medicine The University Of Tokyo
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Yamano Katsuhiro
Biopharmaceutical And Pharmacokinetic Research Laboratories Fujisawa Pharmaceutical Co. Ltd.
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