Visual Overview
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.
Footnotes
- Received December 3, 2014.
- Accepted March 24, 2015.
Karen J. Gregory is a recipient of a National Health and Medical Research Council of Australia (NHMRC) Overseas Biomedical Postdoctoral Training Fellowship; work in her laboratory is supported by a NHMRC project grant [1084775]. Research on metabotropic glutamate receptors in the Conn laboratory is supported by the National Institutes of Health National Institute of Mental Health [Grant R01-MH062646-13], National Institute of Neurological Diseases and Stroke [Grant R01-NS031373-16A2], and National Institute of Drug Abuse [Grant R01-DA023947].
↵This article has supplemental material available at molpharm.aspetjournals.org.
- Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics
MolPharm articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|