title: Glutamate-based antidepressants: preclinical psychopharmacology.
abstract: Over the past 20 years, converging lines of evidence have both linked glutamatergic dysfunction to the pathophysiology of depression and demonstrated that the glutamatergic synapse presents multiple targets for developing novel antidepressants. The robust antidepressant effects of the N-methyl-D-aspartate receptor antagonists ketamine and traxoprodil provide target validation for this family of ionotropic glutamate receptors. This article reviews the preclinical evidence that it may be possible to develop glutamate-based antidepressants by not only modulating ionotropic (N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid) and metabotropic glutamate (mGlu) receptors, including mGlu2/3, mGLu5 and mGlu7 receptors, but also by altering synaptic concentrations of glutamate via specialized transporters such as glial glutamate transporter 1 (excitatory amino-acid transporter 2).
authors: Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland. nfpilc@cyf-kr.edu.pl
authors: Andrzej
authors: A
authors: Pilc
authors: Joanna M
authors: JM
authors: Wierońska
authors: Phil
authors: P
authors: Skolnick
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003866:Depressive Disorder / Q000188:drug therapy*; D004353:Drug Evaluation, Preclinical; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D011600:Psychopharmacology
chemical_list: D000928:Antidepressive Agents; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid