Metabotropic glutamate receptor 2
|Glutamate receptor, metabotropic 2|
|RNA expression pattern|
L-glutamate is the major excitatory neurotransmitter in the central nervous system and activates both ionotropic and metabotropic 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 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 GRM1 and GRM5 and these receptors have been shown to activate phospholipase C. Group II includes GRM2 (this receptor) and GRM3 while Group III includes GRM4, GRM6, GRM7 and GRM8. Group II and III receptors are linked to the inhibition of the cyclic AMP cascade but differ in their agonist selectivities.
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 antidepressant drugs.
- 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.
- LY-487,379: devoid of orthosteric activity; along with related 3-pyridylmethylsulfonamides the first subtype-2-selective potentiator published (2003).
- 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
- RO4491533 - 4-[3-(2,6-dimethylpyridin-4-yl)phenyl]-7-methyl-8-trifluoromethyl-1,3-dihydrobenzo[b][1,4]diazepin-2-one