Design of potent GlyT1 inhibitors: In vitro and in vivo profiles

J Bridges, Richard Williams, C.W. Lindsley

Research output: Contribution to journalArticle

44 Citations (Scopus)


Inhibitors of Gly transporter type-1 (GlyT1) for the treatment of schizophrenia have been pursued on the basis of the NMDA receptor (R) hypofunction hypothesis, which stems largely from the observation that NMDAR antagonists induce symptoms that more closely mimic those characteristic of schizophrenia than do other classes of psychotic agents. GlyT1 is responsible for uptake of synaptic Gly, an NMDAR co-agonist amino acid, in neuronal populations throughout the forebrain. GlyT1 inhibition thereby potentiates NMDAR activity by increasing synaptic Gly levels. Correspondingly, a large body of data suggests that GlyT1 inhibitors likely confer more comprehensive symptom alleviation than current antipsychotics. To date, a number of small-molecule GlyT1 inhibitors have been reported by the pharmaceutical industry. Developments in the discovery and characterization of GlyT1 inhibitors are discussed in this review.
Original languageEnglish
Pages (from-to)591-601
Number of pages11
JournalCurrent opinion in molecular therapeutics
Issue number6
Publication statusPublished - Dec 2008

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Molecular Medicine
  • Genetics(clinical)
  • Drug Discovery
  • Pharmacology

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