Metabotropic glutamate receptor 2

Metabotropic glutamate receptor 2 is a is_associated_with::protein that in humans is encoded by the GRM2 is_associated_with::gene.

Function
is_associated_with::L-glutamate is the major excitatory is_associated_with::neurotransmitter in the central nervous system and activates both ionotropic and metabotropic is_associated_with::glutamate receptors. Glutamatergic neurotransmission is involved in most aspects of normal brain function and can be perturbed in many neuropathologic conditions. The metabotropic glutamate receptors are a family of is_associated_with::G protein-coupled receptors, that have been divided into 3 groups on the basis of sequence homology, putative signal transduction mechanisms, and pharmacologic properties. Group I includes is_associated_with::GRM1 and is_associated_with::GRM5 and these receptors have been shown to activate phospholipase C. Group II includes GRM2 (this receptor) and is_associated_with::GRM3 while Group III includes is_associated_with::GRM4, is_associated_with::GRM6, is_associated_with::GRM7 and is_associated_with::GRM8. Group II and III receptors are linked to the inhibition of the is_associated_with::cyclic AMP cascade but differ in their agonist selectivities.

Ligands
The development of subtype-2-selective positive allosteric modulators (PAMs) experienced steady advance in recent years. mGluR2 potentiation is a new approach for the treatment of schizophrenia. On the other hand, antagonists and negative allosteric modulators of mGluR2/3 have potential as is_associated_with::antidepressant drugs.

PAMs

 * is_associated_with::ADX-71149
 * is_associated_with::GSK1331258
 * Imidazo[1,2-a]pyridines
 * 3-Aryl-5-phenoxymethyl-1,3-oxazolidin-2-ones
 * 3-(Imidazolyl methyl)-3-aza-bicyclo[3.1.0]hexan-6-yl)methyl ethers: potent, orally stable
 * BINA: potent; modest ago-allosteric modulator; robust in-vivo activity.
 * is_associated_with::LY-487,379:  devoid of orthosteric activity; along with related 3-pyridylmethylsulfonamides  the first subtype-2-selective potentiator published (2003).

Antagonists

 * is_associated_with::LY-341,495
 * is_associated_with::MGS-0039

NAMs

 * 7,8-dichloro-4-[3-(2-methylpyridin-4-yl)phenyl]-1,3-dihydro-1,5-benzodiazepin-2-one and related compounds.
 * MNI-137 - 8-bromo-4-(2-cyanopyridin-4-yl)-1H-benzo[b][1,4]diazepin-2(3H)-one
 * is_associated_with::RO4491533 - 4-[3-(2,6-dimethylpyridin-4-yl)phenyl]-7-methyl-8-trifluoromethyl-1,3-dihydrobenzo[b][1,4]diazepin-2-one

Protein-protein interactions
The metabotropic glutamate receptor 2 is able to form a heteromeric complex with its isoform is_associated_with::mGluR4. This heteromer exhibits a pharmacological profile distinct from the parent receptor monomers.