Abstract
Advances in antidepressant therapy have resulted in agents with fewer serious side effects than, for example, nonselective monoamine oxidase inhibitors and tricyclic antidepressants. Nonetheless, these newer agents are far from the ideal. Many of the drawbacks associated with these newer agents--slow onset, low rate of response, and low rate of remission--are likely to be mechanism related. In order to overcome these problems, researchers must either improve upon these traditional, biogenic amine-based mechanisms or explore nontraditional mechanisms. Strategies for improving biogenic amine-based antidepressants include the so-called serotonin augmentation strategy and the broad spectrum agent that simultaneously blocks reuptake at the serotonin, norepinephrine, and dopamine transporters. Two nontraditional approaches employ modulation of glutamate receptor function. At face value, these glutamate-based approaches (N-methyl-D-aspartate [NMDA] antagonists and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid [AMPA] receptor potentiators) appear diametrically opposed. However, these 2 mechanisms may ultimately impact similar cellular endpoints.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Antidepressive Agents / pharmacokinetics
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Antidepressive Agents / pharmacology
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Antidepressive Agents / therapeutic use*
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Biogenic Monoamines / antagonists & inhibitors
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Biogenic Monoamines / metabolism
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Carrier Proteins / drug effects
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Carrier Proteins / metabolism
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Depressive Disorder / drug therapy*
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Depressive Disorder / psychology
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Dopamine Plasma Membrane Transport Proteins
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Down-Regulation / drug effects
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Humans
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Membrane Glycoproteins / drug effects
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Membrane Glycoproteins / metabolism
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Membrane Transport Proteins / drug effects
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Membrane Transport Proteins / metabolism
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Nerve Tissue Proteins / drug effects
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Nerve Tissue Proteins / metabolism
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Norepinephrine Plasma Membrane Transport Proteins
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Rats
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Receptors, AMPA / agonists
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Receptors, AMPA / drug effects
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Receptors, AMPA / metabolism
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Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
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Receptors, N-Methyl-D-Aspartate / drug effects
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Receptors, N-Methyl-D-Aspartate / metabolism
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Receptors, Neurotransmitter / drug effects
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Receptors, Neurotransmitter / metabolism
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Serotonin Plasma Membrane Transport Proteins
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Symporters / drug effects
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Symporters / metabolism
Substances
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Antidepressive Agents
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Biogenic Monoamines
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Carrier Proteins
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Dopamine Plasma Membrane Transport Proteins
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Membrane Glycoproteins
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Membrane Transport Proteins
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Nerve Tissue Proteins
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Norepinephrine Plasma Membrane Transport Proteins
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Receptors, AMPA
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Receptors, N-Methyl-D-Aspartate
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Receptors, Neurotransmitter
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SLC6A2 protein, human
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SLC6A4 protein, human
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Serotonin Plasma Membrane Transport Proteins
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Slc6a2 protein, rat
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Slc6a4 protein, rat
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Symporters