title: Molecular Insights into Metabotropic Glutamate Receptor Allosteric Modulation.
abstract: The metabotropic glutamate (mGlu) receptors are a group of eight family C G protein-coupled receptors that are expressed throughout the central nervous system (CNS) and periphery. Within the CNS the different subtypes are found in neurons, both pre- and/or postsynaptically, where they mediate modulatory roles and in glial cells. The mGlu receptor family provides attractive targets for numerous psychiatric and neurologic disorders, with the majority of discovery programs focused on targeting allosteric sites, with allosteric ligands now available for all mGlu receptor subtypes. However, the development of allosteric ligands remains challenging. Biased modulation, probe dependence, and molecular switches all contribute to the complex molecular pharmacology exhibited by mGlu receptor allosteric ligands. In recent years we have made significant progress in our understanding of this molecular complexity coupled with an increased understanding of the structural basis of mGlu allosteric modulation.
authors: Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences and Department of Pharmacology, Monash University, Parkville, Victoria, Australia (K.J.G.); and Vanderbilt Center for Neuroscience Drug Discovery & Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee (P.J.C).
authors: Karen J
authors: KJ
authors: Gregory
authors: Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences and Department of Pharmacology, Monash University, Parkville, Victoria, Australia (K.J.G.); and Vanderbilt Center for Neuroscience Drug Discovery & Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee (P.J.C) jeff.conn@vanderbilt.edu.
authors: P Jeffrey
authors: PJ
authors: Conn
mesh_terms: D000495:Allosteric Site; D001559:Benzhydryl Compounds / Q000494:pharmacology; D002490:Central Nervous System / Q000378:metabolism* / Q000473:pathology; D015195:Drug Design; D006801:Humans; D058990:Molecular Targeted Therapy; D011487:Protein Conformation; D018094:Receptors, Metabotropic Glutamate / Q000737:chemistry* / Q000378:metabolism
chemical_list: D001559:Benzhydryl Compounds; C507346:N,N'-dibenzhydrylethane-1,2-diamine dihydrochloride; D018094:Receptors, Metabotropic Glutamate