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

Joseph R. Moskal*, Ronald Burch, Jeffrey S. Burgdorf, Roger A. Kroes, Patric K. Stanton, John F. Disterhoft, J. David Leander

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

80 Scopus citations

Abstract

Introduction: 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. Areas covered: 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. Expert opinion: 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.

Original languageEnglish (US)
Pages (from-to)243-254
Number of pages12
JournalExpert Opinion on Investigational Drugs
Volume23
Issue number2
DOIs
StatePublished - Feb 2014

Keywords

  • Antidepressant
  • Depression
  • Glycine site
  • Major depressive disorder
  • NMDA receptor
  • Rapid-acting

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this