Modulation of glutamate receptors: strategies for the development of novel antidepressants.
On a biochemical level, conventional antidepressants have been shown to modulate synaptic levels of biogenic amines (i.e., serotonin, norepinephrine, and dopamine), most often by interfering with reuptake processes or inhibiting metabolism. Strategies directed at modulating glutamatergic transmission may overcome the principal limitations (i.e., delayed onset and low efficacy) that appear to be inherent to these conventional agents. In this brief overview, I summarize two glutamate-based approaches to develop novel antidepressants. These distinct and (on a cellular level) seemingly diametric strategies may converge on intracellular pathways that are also impacted upon by chronic treatment with biogenic amine based agents.
Skolnick
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DOV Pharmaceutical, Inc Hackensack, New Jersey 07601, USA. pskolnick@dovpharm.com
D000818:Animals; D000928:Antidepressive Agents / Q000378:metabolism / Q000627:therapeutic use*; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000378:metabolism / Q000627:therapeutic use*; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D009043:Motor Activity / Q000187:drug effects; D017470:Receptors, Glutamate / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology; D009435:Synaptic Transmission / Q000502:physiology; D013876:Thiophenes / Q000494:pharmacology
D000928:Antidepressive Agents; D018691:Excitatory Amino Acid Antagonists; C434043:LY 392098; D017470:Receptors, Glutamate; D013449:Sulfonamides; D013876:Thiophenes; D018698:Glutamic Acid