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Recent progress in the discovery of non-sarcosine based GlyT1 inhibitors. | LitMetric
The simple amino acid glycine is implicated in both inhibitory and excitatory neurotransmission in mammalian central nervous system, and it modulates excitatory neurotransmission through its role as a necessary co-agonist for glutamatergic N-methyl-D-aspartate (NMDA) receptors. Given the involvement of NMDA receptor-mediated neurotransmission in complex cerebral processes such as cognition, pharmacological manipulation of extracellular synaptic glycine biology is an active area of pharmaceutical research to develop novel treatments for neuropsychiatric disorders. A key component of cerebral glycine metabolism is the glycine transporter type 1 (GlyT1) and elevation of extracellular synaptic glycine concentration by blockade of GlyT1 has been hypothesized to potentiate NMDA receptor function in vivo and to represent a rational approach for the treatment of schizophrenia and cognitive disorders. The present article will review the wealth of scientific evidence supporting that hypothesis and the medicinal chemistry effort by many pharmaceutical companies and academic institutions to develop potent and selective GlyT1 inhibitors.
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