Schizophrenia is a devastating mental illness that afflicts nearly 1% of the world's population. Currently available antipsychotics treat positive symptoms, but are largely ineffective at addressing negative symptoms and cognitive dysfunction. Thus, improved pharmacotherapies that treat all aspects of the disease remain a critical unmet need. There is mounting evidence that links NMDA receptor hypofunction and the expression of schizophrenia, and numerous drug discovery programs have developed agents that directly or indirectly potentiate NMDA receptor-mediated neurotransmission. Several compounds have emerged that show promise for treating all symptom sub-domains in both preclinical models and clinical studies, and we will review recent developments in many of these areas.
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