• Nat Rev Drug Discov · Nov 2013

    Review

    Glycine transporters as novel therapeutic targets in schizophrenia, alcohol dependence and pain.

    • Robert J Harvey and Benjamin K Yee.
    • Department of Pharmacology, University College London School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, UK.
    • Nat Rev Drug Discov. 2013 Nov 1; 12 (11): 866-85.

    AbstractGlycine transporters are endogenous regulators of the dual functions of glycine, which acts as a classical inhibitory neurotransmitter at glycinergic synapses and as a modulator of neuronal excitation mediated by NMDA (N-methyl-D-aspartate) receptors at glutamatergic synapses. The two major subtypes of glycine transporters, GlyT1 and GlyT2, have been linked to the pathogenesis and/or treatment of central and peripheral nervous system disorders, including schizophrenia and related affective and cognitive disturbances, alcohol dependence, pain, epilepsy, breathing disorders and startle disease (also known as hyperekplexia). This Review examines the rationale for the therapeutic potential of GlyT1 and GlyT2 inhibition, and surveys the latest advances in the biology of glycine reuptake and transport as well as the drug discovery and clinical development of compounds that block glycine transporters.

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