NYMC Faculty Publications

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

Author Type(s)

Faculty

DOI

10.1517/13543784.2014.852536

Journal Title

Expert Opinion on Investigational Drugs

First Page

243

Last Page

254

Document Type

Article

Publication Date

2-1-2014

Department

Cell Biology and Anatomy

Second Department

Pharmacology

Keywords

Animals, Antidepressive Agents, Cognition, Depression, Excitatory Amino Acid Agonists, Glycine, Humans, Oligopeptides, Receptors, N-Methyl-D-Aspartate, Treatment Outcome

Disciplines

Medicine and Health Sciences

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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