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	Chlorpromazine oligomer is a potentially active substance that inhibits human D-amino acid oxidase, product of a susceptibility gene for schizophrenia
掲載誌名	正式名：JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY ISSNコード：14756366
出版社	INFORMA HEALTHCARE
巻・号・頁	23(6),901-911頁
著者・共著者	Sanae Iwana,Tomoya Kawazoe,Hwan Ki. Park,Koichiro Tsuchiya,Koji Ono,Kazuko Yorita,Takashi Sakai,Takenori Kusumi,Kiyoshi Fukui
発行年月	2008
概要	D-Amino acid oxidase (DAO), a potential risk factor for schizophrenia, has been proposed to be involved in the decreased glutamatergic neurotransmission in schizophrenia. Here we show the inhibitory effect of an antipsychotic drug, chlorpromazine, on human DAO, which is consistent with previous reports using porcine DAO, although human DAO was inhibited to a lesser degree (Ki=0.7mM) than porcine DAO. Since chlorpromazine is known to induce phototoxic or photoallergic reactions and also to be transformed into various metabolites, we examined the effects of white light-irradiated chlorpromazine on the enzymatic activity. Analytical methods including high-resolution mass spectrometry revealed that irradiation triggered the oligomerization of chlorpromazine molecules. The oligomerized chlorpromazine showed a mixed type inhibition with inhibition constants of low micromolar range, indicative of enhanced inhibition. Taken together, these results suggest that oligomerized chlorpromazine could act as an active substance that might contribute to the therapeutic effects of this drug.
DOI	10.1080/14756360701745478