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The effect of risperidone on D-amino acid oxidase activity as a hypothesis for a novel mechanism of action in the treatment of schizophrenia
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-PK1). 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-PK1 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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Reference:
Benzisoxazole – Wikipedia,
,Benzisoxazole – an overview | ScienceDirect Topics