Recent Developments in Glycine Transporter-1 Inhibitors

Publisher Summary This chapter discusses the recent developments made in glycine transporter–1 inhibitor. The growing body of evidence implicating N -methyl-D-aspartate (NMDA) glutamate receptor hypofunction as an underlying cause of schizophrenia has led to a paradigm shift in the search for safer and more efficacious antipsychotics. The symptoms of schizophrenia generally appear in late adolescence or early adulthood and can be grouped into three specific categories. These include positive symptoms, negative symptoms, and cognitive dysfunction. The inhibition of GlyT-1 provides an attractive means to potentiate NMDA receptor function because of its distribution within the forebrain and colocalization with the receptor. In addition, inhibition of GlyT-1 has garnered a great deal of interest by the pharmaceutical industry resulting in a competitive landscape with several structurally diverse sarcosine-based and nonsarcosine-based inhibitors reported. The growing body of evidence implicating NMDA glutamate receptor hypofunction as an underlying cause of schizophrenia has led to a paradigm shift in the search for safer and more efficacious antipsychotics. The inhibition of GlyT-1 provides an attractive means to potentiate NMDA receptor function because of its distribution within the forebrain and colocalization with the receptor.