title: Metabotropic glutamate receptors: their therapeutic potential in anxiety.
abstract: Psychiatric and neurological disorders are linked to changes in synaptic excitatory processes with a key role for glutamate, that is, the most abundant excitatory amino-acid. Molecular cloning of the metabotropic glutamate (mGlu) receptors has led to the identification of eight mGlu receptors, which, in contrast to ligand-gated ion channels (responsible for fast excitatory transmission), modulate and fine-tune the efficacy of synaptic transmission. mGlu receptors are G protein-coupled and constitute a new group of "drugable" targets for the treatment of various CNS disorders. The recent discovery of small molecules that selectively bind to receptors of Groups I (mGlu1 and mGlu5) and II (mGlu2 and mGlu3) allowed significant advances in our understanding of the roles of these receptors in brain function and dysfunction including anxiety. Although investigation of the role of the Group III (mGlu4, 6, 7, and 8) receptors is less advanced, the generation of genetically manipulated animals and recent advances in the identification of subtype-selective compounds have revealed some first insights into the therapeutic potential of this group of receptors.
authors.affiliation: CNS Disease Biology Area, pRED, Building 74/3W308, Basel CH-4070, Switzerland. will.spooren@roche.com
authors.forename: Will
authors.initials: W
authors.lastname: Spooren
authors.forename: Anne
authors.initials: A
authors.lastname: Lesage
authors.forename: Hilde
authors.initials: H
authors.lastname: Lavreysen
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Gasparini
authors.forename: Thomas
authors.initials: T
authors.lastname: Steckler
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001008:Anxiety Disorders / Q000188:drug therapy* / Q000378:metabolism*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002867:Chromones / Q000494:pharmacology; D006801:Humans; D058446:Ligand-Gated Ion Channels / Q000378:metabolism; D010621:Phenazopyridine / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors* / Q000145:classification / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: C117789:7-(hydroxyimino)cyclopropan(b)chromen-1a-carbxoylic acid ethyl ester; D014151:Anti-Anxiety Agents; D002867:Chromones; D058446:Ligand-Gated Ion Channels; D011725:Pyridines; D018094:Receptors, Metabotropic Glutamate; C120147:SIB 1757; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3; C113897:metabotropic glutamate receptor 6; C102719:metabotropic glutamate receptor 7; C121465:6-methyl-2-(phenylethynyl)pyridine; D010621:Phenazopyridine; C108823:metabotropic glutamate receptor 4