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Rev Bras Psiquiatr. 2005 Sep;27(3):243-8. Epub 2005 Oct 4.

Glutamate modulators as novel interventions for mood disorders.

Author information

1
Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029, USA. sanjay.mathew@mssm.edu

Abstract

Recent evidence suggests that critical molecules in neurotrophic signaling cascades are long-term targets for currently available monoaminergic antidepressants. As chronic and severe mood disorders are characterized by impairments in neuronal resilience, pharmacological strategies that subserve a neuroprotective function might alter disorder pathophysiology and modify disease progression. Several promising approaches involve modulation of the glutamate neurotransmitter system, via post-synaptic receptor blockade or potentiation and presynaptic vesicular release inhibition. A focused review of the extant scientific literature was conducted, with a discussion of 3 compounds or classes of drugs currently undergoing clinical investigation: ketamine, riluzole, and AMPA receptor potentiators. Recent investigations in mood disordered patients suggest that the NMDA receptor antagonist ketamine might demonstrate rapid antidepressant properties. Riluzole has been shown to reverse glutamate-mediated impairments in neuronal plasticity and to stimulate the synthesis of brain derived neurotrophic factor. Open-label trials in treatment-resistant depression have yielded promising results. Likewise, AMPA receptor potentiators favorably impact neurotrophic factors as well as enhance cognition.

CONCLUSIONS:

Pharmacological approaches that modulate components of the glutamate system offer novel targets for severe, recurrent mood disorders. Controlled studies are necessary.

PMID:
16224615
DOI:
/S1516-44462005000400016
[Indexed for MEDLINE]
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