title: Glutamate-Based Drug Discovery for Novel Antidepressants.
abstract: BACKGROUND
  Classic antidepressants that modulate monoaminergic systems are not sufficiently effective and require long systematic application. Recent studies suggest that substances that modulate glutamatergic system may produce an antidepressant effect which is not only faster but also more sustained.
  
  
  METHODS
  In this paper, the authors summarize the results of studies on antidepressant action of ketamine in patients with severe refractory depression, which have demonstrated high efficacy in a very short time after a single dose. Due to the adverse effects of ketamine that substantially exclude it from the daily use by patients, efforts have been made to find other NMDA receptor antagonists, which could mimic the therapeutic effect of ketamine but without the side effects. Intensive studies to elucidate ketamine's mechanism of antidepressant action have also been conducted. Herein, the results of research showing that metabotropic glutamate (mGlu) receptors could be the target of novel antidepressants are also presented.
  
  
  CONCLUSIONS
  The intensive preclinical and clinical research on NMDA and mGlu receptor ligands, which is currently going on, could contribute to the awaited breakthrough in the field of novel antidepressant drug discovery. This line of research may also lead to a new understanding of the biological basis of depression.
authors.affiliation: a Department of Neurobiology , Institute of Pharmacology, Polish Academy of Sciences , Krakow , Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Pałucha-Poniewiera
authors.affiliation: a Department of Neurobiology , Institute of Pharmacology, Polish Academy of Sciences , Krakow , Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Pilc
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000009:adverse effects / Q000494:pharmacology*; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000503:physiopathology; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D007649:Ketamine / Q000009:adverse effects / Q000494:pharmacology; D058990:Molecular Targeted Therapy; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013997:Time Factors
chemical_list: D000928:Antidepressive Agents; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D007649:Ketamine
keywords: Depression; NMDA receptors; glutamate; mGlu2/3 receptors; mGlu5 receptors; mGlu7 receptors