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New strategies for treatment of schizophrenia covers Agonists at the glycine and glutamate site of NMDA receptors include the naturally occurring amino acids glycine and D-serine. An analogue of D-serine, called D-cycloserine is also active at the glycine co-agonist site of NMDA receptors. All of these agents have been tested in schizophrenia with evidence that they can reduce negative and/or cognitive symptoms. The GLY-T1 reuptake pump is the major route of inactivation of synaptic glycine, so it is logical to explore the ability of GLY-T1 inhibitors to enhance synaptic actions of glycine, and, thus, of NMDA receptors. GLY-T1 pumps inhibit reuptake of other neurotransmitters which are blocked by a GLY-T1 inhibitor and this increases the synaptic availability of glycine and thus enhances NMDA neurotransmission.
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