オノ　コウジ   ONO Koji   小野　公嗣    所属   埼玉医科大学  保健医療学部 臨床検査学科    職種   准教授
論文種別	学術雑誌(原著)
言語種別	英語
査読の有無	査読あり
表題	The effect of risperidone on D-amino acid oxidase activity as a hypothesis for a novel mechanism of action in the treatment of schizophrenia
掲載誌名	正式名：JOURNAL OF PSYCHOPHARMACOLOGY ISSNコード：02698811
出版社	SAGE PUBLICATIONS LTD
巻・号・頁	24(7),1055-1067頁
著者・共著者	R. M. Abou El-Magd,H. K. Park,T. Kawazoe,S. Iwana,K. Ono,S. P. Chung,M. Miyano,K. Yorita,T. Sakai,K. Fukui
発行年月	2010/07
概要	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.
DOI	10.1177/0269881109102644