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

Overview

Journal Expert Opin Investig Drugs

Specialty Pharmacology

Date 2013 Nov 21

PMID 24251380

Citations 65

Authors

Joseph R Moskal

Ronald Burch

Jeffrey S Burgdorf

Roger A Kroes

Patric K Stanton

John F Disterhoft

J David Leander

Affiliations

Soon will be listed here.

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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