title: Glycine transporters as novel therapeutic targets in schizophrenia, alcohol dependence and pain.
abstract: Glycine 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.
authors.affiliation: Department of Pharmacology, University College London School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, UK.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Harvey
authors.forename: Benjamin K
authors.initials: BK
authors.lastname: Yee
mesh_terms: D000437:Alcoholism / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D015507:Drugs, Investigational / Q000494:pharmacology / Q000627:therapeutic use*; D005998:Glycine / Q000502:physiology; D050487:Glycine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D008959:Models, Neurological; D058990:Molecular Targeted Therapy / Q000379:methods*; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D015507:Drugs, Investigational; D050487:Glycine Plasma Membrane Transport Proteins; D005998:Glycine