Novel Pharmacologic Targets for the Treatment of Negative Symptoms in Schizophrenia

While positive symptoms of schizophrenia tend to respond well to antipsychotic therapy, negative symptoms remain refractory in many patients. Evidence for N-methyl-d-aspartate (NMDA) glutamate receptor hypofunction in patients with schizophrenia has led to establishing novel treatment targets for resolving those symptoms. This activity reviews glutamatergic agents in the treatment of negative and cognitive symptoms, including the NMDA receptor agonists and partial agonists glycine, d-serine, and d-cycloserine; the glycine transporter inhibitors sarcosine and RG1678; and ampakines, positive allosteric modulators of AMPA glutamate receptors.