R231857

R231857 is a **selective glycine transporter 1 (GlyT1) inhibitor** that was developed as a small molecule investigational drug for the treatment of schizophrenia. By inhibiting the reuptake of glycine in the central nervous system, R231857 aims to enhance glycine-mediated neurotransmission at NMDA (N-methyl-D-aspartate) receptors, which is hypothesized to improve cognitive and psychomotor function in disorders characterized by NMDA receptor hypofunction, such as schizophrenia. R231857 showed increased extracellular glycine levels in preclinical animal studies and demonstrated efficacy in some animal models relevant to schizophrenia, including normalization of prepulse inhibition and reduction of amphetamine-induced hyperactivity. In phase 1 studies in healthy volunteers, it was well-tolerated but failed to produce consistent pharmacodynamic effects, likely due to low CNS exposure at the administered doses. Further clinical efficacy in patients had not been established, and no evidence was found for continued development.