Abstract
D-amino acid oxidase (DAAO) catalyzes the oxidation of D-amino acids including d-serine, a full agonist at the glycine site of the NMDA receptor. A series of benzo[ d]isoxazol-3-ol derivatives were synthesized and evaluated as DAAO inhibitors. Among them, 5-chloro-benzo[ d]isoxazol-3-ol (CBIO) potently inhibited DAAO with an IC50 in the submicromolar range. Oral administration of CBIO in conjunction with d-serine enhanced the plasma and brain levels of d-serine in rats compared to the oral administration of d-serine alone.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Administration, Oral
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Animals
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Benzoxazoles / chemical synthesis*
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Benzoxazoles / chemistry
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Benzoxazoles / pharmacology
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Brain / metabolism
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D-Amino-Acid Oxidase / antagonists & inhibitors*
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Drug Synergism
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Isoxazoles / chemical synthesis*
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Isoxazoles / chemistry
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Isoxazoles / pharmacology
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Male
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Rats
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Rats, Sprague-Dawley
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Serine / administration & dosage
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Serine / metabolism
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Serine / pharmacology
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Structure-Activity Relationship
Substances
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5-chlorobenzo(d)isoxazol-3-ol
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Benzoxazoles
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Isoxazoles
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Serine
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D-Amino-Acid Oxidase