Metabotropic glutamate receptor 5-negative allosteric modulators for the treatment of psychiatric and neurological disorders (2009-July 2013).
Negative allosteric modulators of metabotropic glutamate receptor 5 (mGlu5) have been actively pursued for over a decade as a potential treatment for anxiety, depression, substance abuse, pain, levodopa-induced dyskinesia in Parkinson's disease, fragile X Syndrome, autism, gastroesophageal reflux disease and lower-urinary-tract disorders. This article begins with an introduction of preclinical validation of potential therapies for psychiatric and neurological disorders, and of clinical results, followed by a comprehensive overview of the mGlu5-negative allosteric modulator patent applications published between 2009 and July 2013, with a focus on the analysis of structure and in silico CNS drug-like properties of example compounds and disclosed data. Given positive results in proof-of-concept studies in humans for certain indications such as levodopa-induced dyskinesia in Parkinson's disease, fragile X Syndrome, gastroesophageal reflux disease, migraine and anxiety, and the soaring chemical diversity among the mGlu5-negative allosteric modulators, there is reason to believe that a drug will emerge from this therapeutic class in the near future.
Discovery Chemistry & DMPK, Lundbeck Research USA, 215 College Rd., Paramus, NJ 07661, USA. guli@lundbeck.com.
Guiying
G
Li
Morten
M
Jørgensen
Brian M
BM
Campbell
D000818:Animals; D006801:Humans; D001523:Mental Disorders / Q000188:drug therapy* / Q000378:metabolism; D009422:Nervous System Diseases / Q000188:drug therapy* / Q000378:metabolism; D010330:Patents as Topic; D064529:Receptor, Metabotropic Glutamate 5 / Q000378:metabolism*
D064529:Receptor, Metabotropic Glutamate 5