Glutamate modulators as novel interventions for mood disorders

Revista Brasileira de Psiquiatria

Sanjay J Mathew¹  Kathryn Keegan¹  Lisa Smith¹ 

[1] ,Mount Sinai School of Medicine Department of Psychiatry New York NY

关键词: Mood disorders;    Signal transduction;    Antidepressive agents;    Glutamates;    Ketamine;    Riluzole;    Receptors;    AMPA;    Transtornos do humor;    Transdução de sinal;    Antidepressivos;    Glutamatos;    Ketamina;    Riluzol;    Receptores de AMPA;   

DOI  :  10.1590/S1516-44462005000300016

来源: SciELO

【 摘 要 】

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.

【 授权许可】

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