Enhancing AMPA to NMDA throughput as a convergent mechanism for antidepressant action

Jing Du; Rodrigo Machado-Vieira; Sungho Maeng; Keri Martinowich; Husseini K. Manji; Carlos A. Zarate

doi:10.1016/j.ddstr.2006.11.012

Enhancing AMPA to NMDA throughput as a convergent mechanism for antidepressant action

Jing Du, Rodrigo Machado-Vieira, Sungho Maeng, Keri Martinowich, Husseini K. Manji, Carlos A. Zarate

Research output: Contribution to journal › Review article › peer-review

41 Scopus citations

Abstract

In this article, we first review current knowledge of the AMPA and NMDA glutamate receptors, their physiological properties and functions and their regulation by signaling cascades. We then discuss our hypothesis that the therapeutic effects of monoaminergic antidepressants and ketamine, an NMDA receptor antagonist, may be mediated by increased AMPA to NMDA throughput in critical neuronal circuits. We hypothesize that ketamine mediates this throughput directly, thus resulting in rapid antidepressant effects whereas monoaminergic antidepressants work indirectly and gradually; this may explain, in part, the delayed onset of several weeks to months that is observed with traditional antidepressants.

Original language	English (US)
Pages (from-to)	519-526
Number of pages	8
Journal	Drug Discovery Today: Therapeutic Strategies
Volume	3
Issue number	4
DOIs	https://doi.org/10.1016/j.ddstr.2006.11.012
State	Published - Jun 2006
Externally published	Yes

ASJC Scopus subject areas

Molecular Medicine
Pharmacology
Drug Discovery

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10.1016/j.ddstr.2006.11.012

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abstract = "In this article, we first review current knowledge of the AMPA and NMDA glutamate receptors, their physiological properties and functions and their regulation by signaling cascades. We then discuss our hypothesis that the therapeutic effects of monoaminergic antidepressants and ketamine, an NMDA receptor antagonist, may be mediated by increased AMPA to NMDA throughput in critical neuronal circuits. We hypothesize that ketamine mediates this throughput directly, thus resulting in rapid antidepressant effects whereas monoaminergic antidepressants work indirectly and gradually; this may explain, in part, the delayed onset of several weeks to months that is observed with traditional antidepressants.",

author = "Jing Du and Rodrigo Machado-Vieira and Sungho Maeng and Keri Martinowich and Manji, {Husseini K.} and Zarate, {Carlos A.}",

note = "Funding Information: This study was supported by the Intramural Research Program at the National Institute of Mental Health, National Institutes of Health, and Department of Health & Human Services, The Stanly Medical Research Institute and NARSAD. ",

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AU - Du, Jing

AU - Machado-Vieira, Rodrigo

AU - Maeng, Sungho

AU - Martinowich, Keri

AU - Manji, Husseini K.

AU - Zarate, Carlos A.

N1 - Funding Information: This study was supported by the Intramural Research Program at the National Institute of Mental Health, National Institutes of Health, and Department of Health & Human Services, The Stanly Medical Research Institute and NARSAD.

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N2 - In this article, we first review current knowledge of the AMPA and NMDA glutamate receptors, their physiological properties and functions and their regulation by signaling cascades. We then discuss our hypothesis that the therapeutic effects of monoaminergic antidepressants and ketamine, an NMDA receptor antagonist, may be mediated by increased AMPA to NMDA throughput in critical neuronal circuits. We hypothesize that ketamine mediates this throughput directly, thus resulting in rapid antidepressant effects whereas monoaminergic antidepressants work indirectly and gradually; this may explain, in part, the delayed onset of several weeks to months that is observed with traditional antidepressants.

AB - In this article, we first review current knowledge of the AMPA and NMDA glutamate receptors, their physiological properties and functions and their regulation by signaling cascades. We then discuss our hypothesis that the therapeutic effects of monoaminergic antidepressants and ketamine, an NMDA receptor antagonist, may be mediated by increased AMPA to NMDA throughput in critical neuronal circuits. We hypothesize that ketamine mediates this throughput directly, thus resulting in rapid antidepressant effects whereas monoaminergic antidepressants work indirectly and gradually; this may explain, in part, the delayed onset of several weeks to months that is observed with traditional antidepressants.

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Enhancing AMPA to NMDA throughput as a convergent mechanism for antidepressant action

Abstract

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