2010年7月
The effect of risperidone on D-amino acid oxidase activity as a hypothesis for a novel mechanism of action in the treatment of schizophrenia
JOURNAL OF PSYCHOPHARMACOLOGY
- ,
- ,
- ,
- ,
- ,
- ,
- ,
- ,
- ,
- 巻
- 24
- 号
- 7
- 開始ページ
- 1055
- 終了ページ
- 1067
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1177/0269881109102644
- 出版者・発行元
- SAGE PUBLICATIONS LTD
D-Amino acid oxidase (DAO) has been established to be involved in the oxidation of D-serine, an allosteric activator of the N-methyl-D-aspartate-type glutamate receptor in the brain, and to be associated with the onset of schizophrenia. The effect of risperidone, a benzisoxazole derivative, atypical antischizophrenic drug, on the activity of human DAO was tested using an in-vitro oxygraph system and rat C6, stable C6 transformant cells overexpressing mouse DAO (designated as C6/DAO) and pig kidney epithelial cells (LLC-PK(1)). Risperidone has a hyperbolic mixed- type inhibition, designated as 'partial uncompetitive inhibition effect', with K(i) value of 41 mu M on human DAO. Risperidone exhibited a protective effect from D-amino acid induced cell death in both C6/DAO and LLC-PK(1) cells with 10% increase in viability. These data indicate the involvement of DAO activity in D-serine metabolism and also suggest a new mechanism of action to risperidone as antischizophrenic drug.
- リンク情報
- ID情報
-
- DOI : 10.1177/0269881109102644
- ISSN : 0269-8811
- Web of Science ID : WOS:000278866900013