TY - JOUR
T1 - Potential psychiatric applications of metabotropic glutamate receptor agonists and antagonists
AU - Krystal, John H.
AU - Mathew, Sanjay J.
AU - Dsouza, D. Cyril
AU - Garakani, Amir
AU - Gunduz-Bruce, Handan
AU - Charney, Dennis S.
N1 - Funding Information:
This work was generously supported by Department of Veterans Affairs (via support for the Alcohol Research Center, Merit Review Grant, National Center for PTSD), the National Institute on Alcohol Abuse and Alcoholism (RO1 AA-11321, K05 AA-14906-01, I-P50 AA-12870), the National Institute of Mental Health (MH P50 MH44866, P50 MH068789, K23-MH-069656), NARSAD and the Yale Center for Clinical Investigation (CTSA).
PY - 2010
Y1 - 2010
N2 - 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.
AB - 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.
KW - Anxiety-disorders
KW - Bipolar-disorders
KW - Depression
KW - Metabotropic-glutamate- receptor-agonists, general
KW - Metabotropic-glutamate-receptor-antagonists, general
KW - Metabotropic-glutamate-receptor-modulators, general
KW - Schizophrenia
UR - http://www.scopus.com/inward/record.url?scp=77955048810&partnerID=8YFLogxK
U2 - 10.2165/11533230-000000000-00000
DO - 10.2165/11533230-000000000-00000
M3 - Review article
C2 - 20658799
AN - SCOPUS:77955048810
SN - 1172-7047
VL - 24
SP - 669
EP - 693
JO - CNS Drugs
JF - CNS Drugs
IS - 8
ER -