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Description

A cell-permeable benzisoxazolone compound that potently inhibits D-amino acid oxidase (DAO/DAAO/DAMOX/OXDA) activity (IC50 = 90 and 150/188 nM against rat spinal cord and porcine kidney DAO, respectively) in a reversible and D-serine-competitive (Ki = 100 nM) manner. Upon co-administration, CBIO (30 mg/kg, p.o.) markedly prolongs the half-life of orally administered D-serine (30 mg/kg) in plasma, resulting in enhanced rat brain D-serine level (60% vs. 25% above basal, respectively, with vs. without CBIO). Direct intrathecal/spinal CBIO injection either before (ED50 =60 ng) or after (ED50 = 170 ng) subcutaneous formalin injection (50 µ,l 5% solution) greatly alleviates formalin-induced late phase tonic pain (Emax =67%), but not early phase acute nociception in rats in vivo.