title: mGluR2 positive allosteric modulators: a patent review (2009 - present).
abstract: BACKGROUND
  The mGlu2 receptor, which belongs to the group II subfamily of metabotropic glutamate receptors (mGlu) along with the mGlu3 receptor, has proven to be of particular importance in neuropharmacology. Preferentially expressed on presynaptic nerve terminals, the mGlu2 receptor negatively modulates glutamate and GABA release and is widely distributed in the brain. High levels of mGlu2 receptors are seen in brain areas such as prefrontal cortex, hippocampus and amygdala where glutamate hyperfunction may be implicated in disorders and diseases such as anxiety and schizophrenia. Given the promise offered by mGlu2/3 receptor activation, there is increased interest in identifying small molecules which activate the receptor. A preferred approach is via positive allosteric modulators (PAMs) which bind at an alternative site to agonists.
  
  
  METHODS
  This review covers the patent applications which were published between April 2009 and December 2012 on PAMs of the mGlu2, and it is a continuation of an earlier review published in this journal.
  
  
  CONCLUSIONS
  Advances in medicinal chemistry and pharmacology have set the stage in the field of mGlu2 receptor PAMs. Compounds currently advancing in clinical trials will soon establish the therapeutic potential of this allosteric approach.
authors: Janssen Research and Development, Neuroscience Medicinal Chemistry Department, Toledo, Spain. atrabanc@its.jnj.com
authors: Andrés A
authors: AA
authors: Trabanco
authors: José María
authors: JM
authors: Cid
mesh_terms: D000494:Allosteric Regulation / Q000187:drug effects; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D015195:Drug Design; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D010330:Patents as Topic; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects* / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid