Metabotropic Glutamate Receptors

Glutamate receptors consist of two families, the ionotrophic receptors which include NMDA, AMPA and Kainate receptors and the metabotropic receptors.

The metabotropic glutamate (mGlu) receptors are G-protein coupled receptors, which consist of 8 members arranged into 3 groups. Group I is comprised of mGlu 1 and 5, which is coupled to Gq/o and intracellular calcium. Group II (mGlu 2 and 3) and Group III (mGlu 4, 6, 7 and 8) are coupled to Gi and reduce cAMP. These receptors have a very large extracellular domain, the so called venus fly trap domain, which binds the endogenous ligand glutamate as well as other orthosteric ligands. In contrast, allosteric ligands bind to the transmembrane domain. The Group II receptors mGlu 2 and 3, which are Braincells main focus of research, are predominantly localized pre or peri-synaptically and function as auto-receptors reducing glutamate release from the pre-synaptic site. In addition, mGlu 3 is also localized on astrocytes.

BrainCells is investigating antagonism of the mGlu2/3 receptors as a potential novel therapy for a variety of central nervous system (CNS) disorders including major depressive disorder (MDD), treatment resistant depression (TRD) and cognitive improvements in Alzheimer’s disease (AD).