Application of Chemical P450 Model Systems to Studies on Drug Metabolism. I. Phencyclidine : A Multi-functional Model Substrate

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Cytochrome P450 model and liver microsomal oxidations of drugs were compared using phencyclidine. In general, the chemical reaction systems produced many oxidation products. Besides the formation of the cyclohexane-4-hydroxyl compound (2), hydroxylation of the aromatic ring was favored in the Fenton reaction system (Fe^<2+>+H_2O_2). Formation of an m-hydroxylated product (m-5) was the main aromatic oxidation pathway in the Udenfriend reaction (Fe^<2+>-ascorbic acid-O_2), and 2,the piperidine-3-hydroxyl compound (3), and the piperidine-4-hydroxyl compound (4) were also formed. In the system using meso-tetraphenylporphinatoiron chloride (Fe(III)TPPC1) with an oxidant, the main product was the piperidine-3-oxo compound (8). In the liver microsomes system, 2,4,8,and m-5,which were all generated by the chemical oxidation reactions, were detected as metabolites of phencyclidine. They were formed by cytochrome P450-dependent reactions. Chemical oxidation systems can be used to study drug metabolism; they can reveal some tendencies of the real metabolis reactions, are easy to operate, and yield sufficient amounts of product.

収録刊行物

  • Chemical & pharmaceutical bulletin   [巻号一覧]

    Chemical & pharmaceutical bulletin 37(7), 1788-1794, 1989-07-25  [この号の目次]

    公益社団法人日本薬学会

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各種コード

  • NII論文ID(NAID)
    110003627858
  • NII書誌ID(NCID)
    AA00602100
  • 本文言語コード
    ENG
  • 資料種別
    雑誌論文
  • ISSN
    00092363
  • データ提供元
    CJP引用  NII-ELS 
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