title: GLYX-13, an NMDA receptor glycine site functional partial agonist enhances cognition and produces antidepressant effects without the psychotomimetic side effects of NMDA receptor antagonists.
abstract: BACKGROUND
  The N-methyl-d-aspartate receptor-ionophore complex plays a key role in learning and memory and has efficacy in animals and humans with affective disorders. GLYX-13 is an N-methyl-d-aspartate receptor (NMDAR) glycine-site functional partial agonist and cognitive enhancer that also shows rapid antidepressant activity without psychotomimetic side effects.
  
  
  METHODS
  The authors review the mechanism of action of GLYX-13 that was investigated in preclinical studies and evaluated in clinical studies. Specifically, the authors review its pharmacology, pharmacokinetics, and drug safety that were demonstrated in clinical studies.
  
  
  CONCLUSIONS
  NMDAR full antagonists can produce rapid antidepressant effects in treatment-resistant subjects; however, they are often accompanied by psychotomimetic effects that make chronic use outside of a clinical trial inpatient setting problematic. GLYX-13 appears to exert its antidepressant effects in the frontal cortex via NMDAR-triggered synaptic plasticity. Understanding the mechanistic underpinning of GLYX-13's antidepressant action should provide both novel insights into the role of the glutamatergic system in depression and identify new targets for therapeutic development.
authors.affiliation: Northwestern University, McCormick School of Engineering and Applied Science, Falk Center for Molecular Therapeutics, Department of Biomedical Engineering , 1801 Maple Avenue, Suite 4300, Evanston IL 60201 , USA j-moskal@northwestern.edu.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Moskal
authors.forename: Ronald
authors.initials: R
authors.lastname: Burch
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Burgdorf
authors.forename: Roger A
authors.initials: RA
authors.lastname: Kroes
authors.forename: Patric K
authors.initials: PK
authors.lastname: Stanton
authors.forename: John F
authors.initials: JF
authors.lastname: Disterhoft
authors.forename: J David
authors.initials: JD
authors.lastname: Leander
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects; D003863:Depression / Q000188:drug therapy*; D018690:Excitatory Amino Acid Agonists / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D005998:Glycine / Q000378:metabolism; D006801:Humans; D009842:Oligopeptides / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists*; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D018690:Excitatory Amino Acid Agonists; D009842:Oligopeptides; D016194:Receptors, N-Methyl-D-Aspartate; C507283:GLYX-13 peptide; D005998:Glycine