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
| Autor: | Joseph R. Moskal, Roger A. Kroes, Ronald M. Burch, J. David Leander, John F. Disterhoft, Jeffrey Burgdorf, Patric K. Stanton |
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| Rok vydání: | 2013 |
| Předmět: |
Glycine
Pharmacology Receptors N-Methyl-D-Aspartate Partial agonist Article chemistry.chemical_compound Cognition Excitatory Amino Acid Agonists Rapastinel Animals Humans Medicine Pharmacology (medical) Excitatory Amino Acid Agonist Depression business.industry General Medicine Psychotomimetic Antidepressive Agents Treatment Outcome chemistry Mechanism of action Synaptic plasticity NMDA receptor Antidepressant medicine.symptom business Oligopeptides medicine.drug |
| Zdroj: | Expert Opinion on Investigational Drugs. 23:243-254 |
| ISSN: | 1744-7658 1354-3784 |
| DOI: | 10.1517/13543784.2014.852536 |
| Popis: | 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.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.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. |
| Databáze: | OpenAIRE |
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