The behavioral and neurochemical effects of a novel D-amino acid Effects of D-Amino Acid Oxidase Inhibitor The Open Clinical Chemistry Journal, 2009, Volume 2 21 oxidase inhibitor compound 8 [4H-thieno [3,2-b]pyrrole-5carboxylic acid

Multiple studies indicate that N-methyl-D-aspartate (NMDA) re-ceptor hypofunction underlies some of the deficits associated with schizophrenia. One approach for improving NMDA recep-tor 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 [4H-thieno [3,2-b]pyrrole-5-carboxylic acid] and compared it with D-serine. Compound 8 is a moderately potent inhibitor of hu-man (IC50, 145 nM) and rat (IC50, 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 de-crease in DAAO activity resulted in a significant (p 0.001) elevation in both plasma (220 % of control) and cerebrospina