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 article

69 Citations (Scopus)

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 1 2014

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N-Methyl-D-Aspartate Receptors
Glycine
Cognition
Antidepressive Agents
Nootropic Agents
Neuronal Plasticity
Ionophores
Expert Testimony
Frontal Lobe
Mood Disorders
Inpatients
Pharmacokinetics
Clinical Trials
Learning
Pharmacology
Depression
Safety
aspartic acid receptor
Therapeutics
Pharmaceutical Preparations

Keywords

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

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

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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.",
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author = "Moskal, {Joseph R.} and Ronald Burch and Burgdorf, {Jeffrey S.} and Kroes, {Roger A.} and Stanton, {Patric K.} and Disterhoft, {John F.} and {David Leander}, J.",
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AU - Moskal, Joseph R.

AU - Burch, Ronald

AU - Burgdorf, Jeffrey S.

AU - Kroes, Roger A.

AU - Stanton, Patric K.

AU - Disterhoft, John F.

AU - David Leander, J.

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N2 - 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.

AB - 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.

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