Potential Psychiatric Applications of Metabotropic Glutamate Receptor Agonists and Antagonists

• Published in: CNS drugs Vol. 24; no. 8; pp. 669 - 693
• Main Authors: Krystal, John H., Mathew, Sanjay J., D’Souza, D. Cyril, Garakani, Amir, Gunduz-Bruce, Handan, Charney, Dennis S.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01-08-2010; Adis International; Wolters Kluwer Health, Inc; Springer Nature B.V
• Subjects: Animal cognition; Animals; Anti-Anxiety Agents - therapeutic use; Antidepressive Agents - therapeutic use; Antipsychotic Agents - therapeutic use; Antipsychotic drugs; Anxiety Disorders - drug therapy; Anxiety Disorders - physiopathology; Biological and medical sciences; Central Nervous System Agents - therapeutic use; Complications and side effects; Dosage and administration; Drug abuse; Drug therapy; Gene expression; Health aspects; Humans; Kinases; Localization; Medical sciences; Medicine; Medicine & Public Health; Mental illness; Metabotropic glutamate receptors; Mice; Mood Disorders - drug therapy; Mood Disorders - physiopathology; Neurobiology; Neurology; Neuropharmacology; Neurosciences; Pharmacology. Drug treatments; Pharmacotherapy; Physiology; Proteins; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Rats; Receptors, Metabotropic Glutamate - agonists; Receptors, Metabotropic Glutamate - antagonists & inhibitors; Receptors, Metabotropic Glutamate - classification; Review Article; Schizophrenia; Schizophrenia - drug therapy; Schizophrenia - physiopathology; Signal transduction; United States; Schizophrenia; NMDA Receptor Antagonist; Anxiety Disorder; NMDA Receptor; Lamotrigine; Human; Drug; Mood disorder; Indication; Treatment efficiency; Anxiety disorder; Pharmacotherapy; Glutamate receptor; Review; Psychosis; Treatment; Metabotropic receptor; Agonist antagonist
• ISSN: 1172-7047; 1179-1934
• DOI: 10.2165/11533230-000000000-00000

Drugs acting at metabotropic glutamate receptors (mGluRs) are among the most promising agents under development for the treatment of psychiatric disorders. The research in this area is at a relatively early stage, as there are no drugs acting at mGluRs that have been approved for the treatment of any psychiatric disorder. However, in the areas of schizophrenia, anxiety disorders and mood disorders, research conducted in animal models appears to translate well into efficacy in human laboratory-based models of psychopathology and in preliminary clinical trials. Further, the genes coding for mGluRs are implicated in the risk for a growing number of psychiatric disorders. This review highlights the best studied mGluR strategies for psychiatry, based on human molecular genetics, studies in animal models and preliminary clinical trials. It describes the potential value of mGluR2 and mGluR5 agonists and positive allosteric modulators for the treatment of schizophrenia. It also reviews evidence that group II mGluR agonists and positive allosteric modulators as well as group I mGluR antagonists might also treat anxiety disorders and some forms of depression, while mGluR2 and group I mGluR antagonists (particularly mGluR5 antagonists) might have antidepressant properties. This review also links growing insights into the role of glutamate in the pathophysiology of these disorders to hypothesized mGluR-related treatment mechanisms.