title: Metabotropic glutamate receptor 4 (mGlu4)-positive allosteric modulators for the treatment of Parkinson's disease: historical perspective and review of the patent literature.
abstract: BACKGROUND
  Metabotropic glutamate receptor 4 (mGlu(4)) is a group III GPCR and has been demonstrated to play a major role in a number of therapeutic areas within the CNS. As the orthosteric site of all glutamate receptors is highly conserved, modulating mGlu(4) via allosteric modulation has emerged as a very attractive mode-of-action and has been validated preclinically in a number of animal models for Parkinson's disease, anxiety, pain, and neuroinflammation.
  
  
  METHODS
  In this review, the patent literature for mGlu(4)-positive allosteric modulators over the past 4 years will be provided. Patents from all companies are discussed and an overview of the chemical matter and relevant biological properties will be given.
  
  
  CONCLUSIONS
  Although there has yet to be an mGlu(4)-positive allosteric modulator progressed into clinical trials, there is a wealth of preclinical data from the primary literature that shows the promise of this emerging target. A number of academic and industry laboratories have recently published exciting patent data covering a multitude of chemical matter. Positive allosteric modulation of mGlu(4) remains one of the more attractive non-dopaminergic therapies for Parkinson's disease, as well as emerging data for other indications such as pain, neuroinflammation, schizophrenia and diabetes, which could potentially make mGlu(4) a significant therapeutic target going forward.
authors.affiliation: Vanderbilt University, Vanderbilt University Medical Center, Vanderbilt Center for Neuroscience Drug Discovery, Department of Chemistry, Nashville, TN 37232, USA.
authors.forename: Craig W
authors.initials: CW
authors.lastname: Lindsley
authors.forename: Corey R
authors.initials: CR
authors.lastname: Hopkins
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000737:chemistry / Q000266:history / Q000494:pharmacology*; D001479:Basal Ganglia / Q000187:drug effects* / Q000378:metabolism; D015195:Drug Design; D018690:Excitatory Amino Acid Agonists / Q000737:chemistry / Q000266:history / Q000494:pharmacology*; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D007880:Legislation, Drug; D015394:Molecular Structure; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism; D010300:Parkinson Disease / Q000188:drug therapy* / Q000266:history / Q000378:metabolism; D010330:Patents as Topic; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists* / Q000378:metabolism; D013329:Structure-Activity Relationship; D016896:Treatment Outcome
chemical_list: D000978:Antiparkinson Agents; D018690:Excitatory Amino Acid Agonists; D018094:Receptors, Metabotropic Glutamate; C108823:metabotropic glutamate receptor 4