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Glutamate system as target for development of novel antidepressants

Published online by Cambridge University Press:  01 February 2013

Mario Catena-Dell'Osso ,
Andrea Fagiolini ,
Francesco Rotella ,
Stefano Baroni  and
Donatella Marazziti
Mario Catena-Dell'Osso*
Affiliation:
Department of Psychiatry, Neurobiology, Farmacology and Biotecnology, University of Pisa, Pisa, Italy
Andrea Fagiolini
Affiliation:
Department of Neuroscience, Division of Psychiatry, University of Siena School of Medicine, Siena, Italy
Francesco Rotella
Affiliation:
Department of Neurological and Psychiatric Sciences, University of Florence, Florence, Italy
Stefano Baroni
Affiliation:
Department of Psychiatry, Neurobiology, Farmacology and Biotecnology, University of Pisa, Pisa, Italy
Donatella Marazziti
Affiliation:
Department of Psychiatry, Neurobiology, Farmacology and Biotecnology, University of Pisa, Pisa, Italy
*
*Address for correspondence: Dr. Mario Catena Dell'Osso, Department of Psychiatry, Neurobiology, Farmacology and Biotecnology, University of Pisa, via Roma, 67, I-56100 Pisa, Italy. (Email [email protected])
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Abstract

Depression is a common psychiatric condition characterized by affective, cognitive, psychomotor, and neurovegetative symptoms that interfere with a person's ability to work, study, deal with interpersonal relationships, and enjoy once-pleasurable activities. After the serendipitous discovery of the first antidepressants, for years the only pharmacodynamic mechanisms explored in the search of novel antidepressants were those related to the 3 main monoamines: serotonin, norepinephrine, and dopamine. New-generation monoaminergic antidepressants, such as selective-serotonin and dual-acting serotonin/norepinephrine reuptake inhibitors, improved treatment and quality of life of depressed patients. Nevertheless, there are still important clinical limitations: the long latency of onset of the antidepressant action; side effects, which can lead to early discontinuation; low rate of response; and high rate of relapse/recurrence. Therefore, in the last several years, the focus of research has moved from monoamines toward other molecular mechanisms, including glutamatergic (Glu) neurotransmission. This review provides a comprehensive overview of the current knowledge on the Glu system and on its relationships with mood disorders. Up to now, N-methyl-D-aspartate (NMDA) receptor antagonists, in particular ketamine, provided the most promising results in preclinical studies and produced a consistent and rapid, although transient, antidepressant effect with a good tolerability profile in humans. Although data are encouraging, more double-blind, randomized, placebo-controlled trials are needed to clarify the real potentiality of ketamine, and of the other Glu modulators, in the treatment of unipolar and bipolar depression.

Keywords

Antidepressantsdepressionglutamate (Glu)ketamineN-methyl-daspartate (NMDA) antagonistsriluzole
Type
Review Articles
Information
CNS Spectrums , Volume 18 , Issue 4 , August 2013 , pp. 188 - 198
Copyright
Copyright © Cambridge University Press 2013 

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