The effect of risperidone on D-amino acid oxidase activity as a hypothesis for a novel mechanism of action in the treatment of schizophrenia

@article{AbouElMagd2010TheEO,
  title={The effect of risperidone on D-amino acid oxidase activity as a hypothesis for a novel mechanism of action in the treatment of schizophrenia},
  author={Rabab M Abou El-Magd and H K Park and Tomoya Kawazoe and Sanae Iwana and Koji Ono and S. P. Chung and Motoshige Miyano and Kazuko Yorita and Takashi Sakai and Kiyoshi Fukui},
  journal={Journal of Psychopharmacology},
  year={2010},
  volume={24},
  pages={1055 - 1067}
}
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… 

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Comments on ‘The effect of risperidone on D-amino acid oxidase activity as a hypothesis for a novel mechanism of action in the treatment of schizophrenia’
  • K. Hashimoto
  • Biology, Psychology
    Journal of psychopharmacology
  • 2010
TLDR
It is reported that, using in vivo microdialysis study of conscious and free-moving animals, treatment of the novel DAAO inhibitor 5-chloro-benzo-3-ol (CBIO) did not alter the extracellular D-serine levels in the frontal cortex of rat and mice (Ferraris et al., 2008; Hashimoto et al, 2009).
D-amino acid oxidase inhibitors as a novel class of drugs for schizophrenia therapy.
TLDR
Current evidence indicates that increasing NMDA receptor function, perhaps by inhibiting DAAO-induced degradation of D-serine may alleviate symptoms in schizophrenic patients, and it has been suggested that co-administration of D -serine with a human D AAO inhibitor may be a more effective means of increasing D- Serine levels in the brain.
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Whether antipsychotic drugs currently prescribed for schizophrenia exert D-amino acid oxidase (DAO)-inhibitory effects is investigated by investigating whether human (h)DAO can metabolize D-kynurenine to produce the fluorescent compound kynurenic acid (KYNA) by using high-performance liquid chromatography with mass spectrometry, and fluorescence Spectrometry.
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This review critically review the neurobiology of DAO, its involvement in schizophrenia, and the therapeutic value ofDAO inhibition and highlights issues that have a broader relevance beyond DAO itself.
Effect of risperidone on plasma d-serine concentration in rats post-administered with d-serine.
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d-Amino Acid Oxidase and d-Aspartate Oxidase
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It is proposed that the “d-amino acid biosystems” play important roles in the authors' bodies and chemicals that modulate the enzymatic activity of DAO and DDO are expected as potent therapeutic drugs for schizophrenia and other mental disorders.
Potential cytotoxic effect of hydroxypyruvate produced from D-serine by astroglial D-amino acid oxidase.
TLDR
It is considered that high dose of extracellular D-serine induced cell death by the production of not only hydrogen peroxide but also HPA as a result of DAO catalytic activity in astroglial cell, and this cytotoxicity of HPA is observed uniquely in ast roglial cells expressing DAO.
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The clinical effects of these compounds are reviewed as are the potential effects of newer novel compounds.
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