Evaluation of human D-amino acid oxidase inhibition by anti-psychotic drugs <i>in vitro </i>
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- Shishikura Miho
- Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Toho University
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- Hakariya Hitomi
- Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Toho University
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- Iwasa Sumiko
- Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Toho University
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- Yoshio Takashi
- Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Toho University
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- Ichiba Hideaki
- Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Toho University
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- Yorita Kazuko
- The Institute for Enzyme Research, The University of Tokushima
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- Fukui Kiyoshi
- The Institute for Enzyme Research, The University of Tokushima
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- Fukushima Takeshi
- Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Toho University
Bibliographic Information
- Other Title
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- Evaluation of human D-amino acid oxidase inhibition by anti-psychotic drugs in vitro
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Abstract
It is of importance to determine whether antipsychotic drugs currently prescribed for schizophrenia exert D-amino acid oxidase (DAO)-inhibitory effects. We first investigated whether human (h)DAO can metabolize D-kynurenine (D-KYN) to produce the fluorescent compound kynurenic acid (KYNA) by using high-performance liquid chromatography with mass spectrometry, and fluorescence spectrometry. After confirmation of KYNA production from D-KYN by hDAO, 8 first- and second-generation antipsychotic drugs, and 6 drugs often prescribed concomitantly, were assayed for hDAO-inhibitory effects by using in vitro fluorometric methods with D-KYN as the substrate. DAO inhibitors 3-methylpyrazole-5-carboxylic acid and 4H-thieno[3,2-b]pyrrole-5-carboxylic acid inhibited KYNA production in a dose-dependent manner. Similarly, the second-generation antipsychotics blonanserin and risperidone were found to possess relatively strong hDAO-inhibitory effects in vitro (5.29 ± 0.47 μM and 4.70 ± 0.17 μM, respectively). With regard to blonanserin and risperidone, DAO-inhibitory effects should be taken into consideration in the context of their in vivo pharmacotherapeutic efficacy.
Journal
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- BioScience Trends
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BioScience Trends 8 (3), 149-154, 2014
International Research and Cooperation Association for Bio & Socio-Sciences Advancement