Glutamate system as target for development of novel antidepressants. (1st February 2013)

• Record Type: Journal Article
• Authors: Catena-Dell'Osso, Mario; Fagiolini, Andrea; Rotella, Francesco; Baroni, Stefano; Marazziti, Donatella
• Is Part Of: CNS spectrums. Volume 18:Number 4(2013:Aug.)
• Page Start: 188
• Page End: 198
• Publication Date: 2013-02-01
• Subjects: Antidepressants, -- depression, -- glutamate (Glu), -- ketamine, -- N-methyl-daspartate (NMDA) antagonists, -- riluzole; Neuropsychiatry -- Periodicals; Nervous system -- Diseases -- Periodicals; Neurology -- Periodicals; 616.8005
• DOI: 10.1017/S1092852912000971
• Languages: English
• ISSNs: 1092-8529

Abstract

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.