The NMDA Receptor as a Therapeutic Target in Major Depressive Disorder

Title: The NMDA Receptor as a Therapeutic Target in Major Depressive Disorder

Volume: 6 Issue: 2

Author(s): Christopher Pittenger, Gerard Sanacora and John H. Krystal

Affiliation:

Keywords: Metabotropic glutamate receptors, NR2A subunit gene, Ketamine, NMDA blockade, EAAT2 glutamate transporters

Abstract: Ample evidence indicates that glutamate homeostasis and neurotransmission are disrupted in major depressive disorder; but the nature of this disruption and the mechanisms by which it contributes to the syndrome are unclear. Likewise, the effect of existing antidepressants on glutamate is unclear, as is the potential of drugs directly targeting glutamatergic neurotransmission to act as novel antidepressant medications. These are areas of active research. Here we review current knowledge of the contribution of the NMDA receptor, one of the several types of glutamate receptor, to depression and its treatment. Several lines of evidence, in humans and in animal models, support the contention that neurotransmission via the NMDA receptor is dysregulated in depression. Drugs that target the NMDA receptor have shown antidepressant properties in both clinical and preclinical studies. Nevertheless, other effects of such medications, including both cognitive side effects and their psychotomimetic properties, complicate such an application and represent a challenge to the development of clinically useful agents.

Cite this article as:

Pittenger Christopher, Sanacora Gerard and Krystal H. John, The NMDA Receptor as a Therapeutic Target in Major Depressive Disorder, CNS & Neurological Disorders - Drug Targets 2007; 6 (2) . https://dx.doi.org/10.2174/187152707780363267