The Behavioral and Neurochemical Effects of a Novel d-Amino Acid Oxidase Inhibitor Compound 8 [4H-Thieno [3,2-b]pyrrole-5-carboxylic Acid] and d-Serine

Multiple studies indicate that N -methyl-d-aspartate (NMDA) receptor hypofunction underlies some of the deficits associated with schizophrenia. One approach for improving NMDA receptor function is to enhance occupancy of the glycine modulatory site on the NMDA receptor by increasing the availability of the endogenous coagonists d-serine. Here, we characterized a novel d-amino acid oxidase (DAAO) inhibitor, compound 8 [4 H -thieno [3,2- b ]pyrrole-5-carboxylic acid] and compared it with d-serine. Compound 8 is a moderately potent inhibitor of human (IC 50 , 145 nM) and rat (IC 50 , 114 nM) DAAO in vitro. In rats, compound 8 (200 mg/kg) decreased kidney DAAO activity by ∼96% and brain DAAO activity by ∼80%. This marked decrease in DAAO activity resulted in a significant ( p