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Glycine Transport Inhibitors in the Treatment of Schizophrenia

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Novel Antischizophrenia Treatments

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 213))

Abstract

Schizophrenia is a severe neuropsychiatric disorder without adequate current treatment. Recent theories of schizophrenia focus on disturbances of glutamatergic neurotransmission particularly at N-methyl-d-aspartate (NMDA)-type glutamate receptors. NMDA receptors are regulated in vivo by the amino acids glycine and d-serine. Glycine levels, in turn, are regulated by glycine type I (GlyT1) transporters, which serve to maintain low subsaturating glycine levels in the vicinity of the NMDA receptor. A proposed approach to treatment of schizophrenia, therefore, is inhibition of GlyT1-mediated transport. Over the past decade, several well tolerated, high affinity GlyT1 inhibitors have been developed and shown to potentiate NMDA receptor-mediated neurotransmission in animal models relevant to schizophrenia. In addition, clinical trials have been conducted with sarcosine (N-methylglycine), a naturally occurring GlyT1 inhibitor, and with the high affinity compound RG1678. Although definitive trials remain ongoing, encouraging results to date have been reported.

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Acknowledgments

Support: This work was supported in part by NIH grants R37 MH049334, P50 MH086385, R01 DA03383 and U01 MH074356.

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  1. Schizophrenia Research, Nathan S Kline Institute for Psychiatric Research, Columbia University, 140 Old Orangeburg Rd, Orangeburg, NY, 10962, USA

    Daniel C. Javitt M.D., Ph.D.

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  1. Daniel C. Javitt M.D., Ph.D.
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Correspondence to Daniel C. Javitt M.D., Ph.D. .

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Editors and Affiliations

  1. Dept. Psychiatry, University of California San Diego, Gilman Drive 9500, La Jolla, 92093-0804, California, USA

    Mark A. Geyer

  2. Institut für Pharmakologie, Universität, Neuroscience Research, Abbott GmbH & Co. KG, Knollstraße, Ludwigshafen, 67061, Germany

    Gerhard Gross

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Javitt, D.C. (2012). Glycine Transport Inhibitors in the Treatment of Schizophrenia. In: Geyer, M., Gross, G. (eds) Novel Antischizophrenia Treatments. Handbook of Experimental Pharmacology, vol 213. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-25758-2_12

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