| The effect of risperidone on D-amino acid oxidase activity as a hypothesis for a novel mechanism of action in the treatment of schizophrenia. | |
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MedLine Citation:
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PMID: 19329549 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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 microM 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. |
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Authors:
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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 |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-03-27 |
Journal Detail:
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Title: Journal of psychopharmacology (Oxford, England) Volume: 24 ISSN: 1461-7285 ISO Abbreviation: J. Psychopharmacol. (Oxford) Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-06-17 Completed Date: 2010-09-16 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8907828 Medline TA: J Psychopharmacol Country: United States |
Other Details:
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Languages: eng Pagination: 1055-67 Citation Subset: IM |
Affiliation:
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Division of Enzyme Pathophysiology, The Institute for Enzyme Research, The University of Tokushima, Tokushima, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antipsychotic Agents / pharmacology*, therapeutic use Apoenzymes / metabolism Apoproteins / chemistry Blotting, Western Catalysis Cell Survival / drug effects Culture Media D-Amino-Acid Oxidase / antagonists & inhibitors* Enzyme Inhibitors* Holoenzymes / metabolism Humans Kinetics LLC-PK1 Cells Mice Rats Receptors, N-Methyl-D-Aspartate / metabolism Recombinant Proteins / metabolism Risperidone / pharmacology*, therapeutic use Schizophrenia / drug therapy*, enzymology* Serine / metabolism Swine |
| Chemical | |
Reg. No./Substance:
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0/Antipsychotic Agents; 0/Apoenzymes; 0/Apoproteins; 0/Culture Media; 0/Enzyme Inhibitors; 0/Holoenzymes; 0/Receptors, N-Methyl-D-Aspartate; 0/Recombinant Proteins; 106266-06-2/Risperidone; 56-45-1/Serine; EC 1.4.3.3/D-Amino-Acid Oxidase |
| Comments/Corrections | |
Comment In:
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J Psychopharmacol. 2010 Jul;24(7):1133-4
[PMID:
19939869
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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