Glutamate-based therapeutic approaches: targeting the glutamate transport system.
Although the ionotropic and metabotropic receptors for synaptically released glutamate have been extensively mined in the pursuit of novel therapeutic agents for a diverse array of central nervous system disorders, pursuit of the transport proteins--or excitatory amino acid transporters (EAATs)--toward a similar end has been a road much less travelled. Recent progress has seen the use of cloned EAAT subtypes to develop transporter inhibitors with improved subtype selectivity, providing important tools for elucidating the precise contribution of each transporter subtype to the regulation of extracellular glutamate homeostasis. In addition, momentum has been gained with the discovery of compounds capable of upregulating the activity of the predominant forebrain glutamate transporter, EAAT2.
Dunlop
John
J
Neuroscience Discovery Research, Wyeth Research, CN-8000, Princeton, New Jersey 08543, USA. Dunlopj@wyeth.com
D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology; D027342:Excitatory Amino Acid Transporter 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D050491:Glutamate Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006536:Heptanes / Q000494:pharmacology*; D006575:Heterocyclic Compounds, 3-Ring / Q000494:pharmacology*; D006801:Humans; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism
C487627:3-aminotricyclo(2.2.1.02.6)heptane-1,3-dicarboxylic acid; D027342:Excitatory Amino Acid Transporter 2; D050491:Glutamate Plasma Membrane Transport Proteins; D006536:Heptanes; D006575:Heterocyclic Compounds, 3-Ring; C120673:benzyloxyaspartate; D001224:Aspartic Acid; D018698:Glutamic Acid