Journal
NATURE REVIEWS DRUG DISCOVERY
Volume 12, Issue 11, Pages 866-885Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nrd3893
Keywords
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Funding
- Medical Research Council [G0500833, G0601585, J004049]
- Action Medical Research [1966]
- US National Institutes of Health (NIH) [R01MH083973]
- Legacy Foundation Grant
- Swiss National Science Foundation [3100-066855]
- Swiss National Center of Competence in Research Neural Plasticity and Repair
- Swiss Federal Institute of Technology, Zurich
- Action Medical Research [1966] Funding Source: researchfish
- Medical Research Council [MR/J004049/1, G0601585, G0500833] Funding Source: researchfish
- MRC [G0500833, MR/J004049/1, G0601585] Funding Source: UKRI
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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.
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