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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.
AuthorsRobert J Harvey, Benjamin K Yee
JournalNature reviews. Drug discovery (Nat Rev Drug Discov) Vol. 12 Issue 11 Pg. 866-85 (Nov 2013) ISSN: 1474-1784 [Electronic] England
PMID24172334 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)
Chemical References
  • Drugs, Investigational
  • Glycine Plasma Membrane Transport Proteins
  • Glycine
Topics
  • Alcoholism (drug therapy, metabolism)
  • Animals
  • Drugs, Investigational (pharmacology, therapeutic use)
  • Glycine (physiology)
  • Glycine Plasma Membrane Transport Proteins (antagonists & inhibitors)
  • Humans
  • Models, Neurological
  • Molecular Targeted Therapy (methods)
  • Pain (drug therapy, metabolism)
  • Schizophrenia (drug therapy, metabolism)
  • Synaptic Transmission (drug effects, physiology)

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