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Pharmaceuticals 2013, 6(4), 480-499; doi:10.3390/ph6040480

NMDA Receptor Antagonists for Treatment of Depression

1,2,*  and 1,*
1 Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy, University of the Sciences in Philadelphia, 600 South 43rd Street, Philadelphia, PA 19104, USA 2 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ankara University, Tandogan 06100, Ankara, Turkey
* Authors to whom correspondence should be addressed.
Received: 31 January 2013 / Revised: 27 March 2013 / Accepted: 27 March 2013 / Published: 3 April 2013
(This article belongs to the Special Issue NMDA Receptor Antagonists for Treatment of CNS Disorders)


Depression is a psychiatric disorder that affects millions of people worldwide. Individuals battling this disorder commonly experience high rates of relapse, persistent residual symptoms, functional impairment, and diminished well-being. Medications have important utility in stabilizing moods and daily functions of many individuals. However, only one third of patients had considerable improvement with a standard antidepressant after 2 months and all patients had to deal with numerous side effects. The N-methyl-d-aspartate (NMDA) receptor family has received special attention because of its critical role in psychiatric disorders. Direct targeting of the NMDA receptor could result in more rapid antidepressant effects. Antidepressant-like effects of NMDA receptor antagonists have been demonstrated in different animal models. MK-801 (a use-dependent channel blocker), and CGP 37849 (an NMDA receptor antagonist) have shown antidepressant properties in preclinical studies, either alone or combined with traditional antidepressants. A recent development is use of ketamine clinically for refractory depression. The purpose of this review is to examine and analyze current literature on the role of NMDA receptor antagonists for treatment of depression and whether this is a feasible route in drug discovery.
Keywords: NMDA receptor antagonists; depression; antidepressant-like effect; ketamine; MK-801; forced swim test NMDA receptor antagonists; depression; antidepressant-like effect; ketamine; MK-801; forced swim test
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Ates-Alagoz, Z.; Adejare, A. NMDA Receptor Antagonists for Treatment of Depression. Pharmaceuticals 2013, 6, 480-499.

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