Glutamate modulators as novel interventions for mood disorders
Mathew SJ, Keegan K, Smith L.
Department of Psychiatry,
Mount Sinai School of Medicine,
New York, NY 10029, USA.
Rev Bras Psiquiatr. 2005 Sep;27(3):243-8.
ABSTRACTRecent 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.
Comfortably numb? (PDF)
Ketamine and opiate withdrawal
Ketamine and the nucleus accumbens
Ketamine: medical and non-medical use
The role of ketamine in pain management
Ketamine racemate versus S-(+)-ketamine and midazolam
Ketamine and the glutaminergic hypothesis of schizophrenia
Low-dose ketamine as a fast-onset, long-acting antidepressant
and further reading
The Abolitionist Project
The Hedonistic Imperative
The Reproductive Revolution
Critique of Huxley's Brave New World
The Good Drug Guide
The Responsible Parent's Guide
To Healthy Mood Boosters For All The Family