RT Journal Article
SR Electronic
T1 Molecular Insights into Metabotropic Glutamate Receptor Allosteric Modulation
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP mol.114.097220
DO 10.1124/mol.114.097220
A1 Karen J Gregory
A1 P. Jeffrey Conn
YR 2015
UL http://molpharm.aspetjournals.org/content/early/2015/03/24/mol.114.097220.abstract
AB The metabotropic glutamate (mGlu) receptors are a group of eight family C G protein-coupled receptors that are expressed throughout the CNS and periphery. Within the CNS the different subtypes are found in neurons, both pre- and/or post-synaptically where they mediate modulatory roles and in glial cells. The mGlu receptor family provides attractive targets for numerous psychiatric and neurological disorders, with the majority of discovery programs focussed 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.