Metabotropic glutamate receptor 2 (mGluR2) (mGluR2)

The metabotropic glutamate receptors 2 and 3 (mGluR2/3) are Class C G protein-coupled receptors that function as presynaptic autoreceptors in the central nervous system (UniProt Q14416, Q14832). Their primary biological role is to inhibit the release of glutamate, thereby modulating excitatory neurotransmission and maintaining synaptic balance (PubMed: 11520919). These receptors were targeted by the drug candidate LY2140023 (pomaglumetad methionil), a prodrug of the active agonist LY404039, for the treatment of schizophrenia (PubChem CID 11370854). The rationale was that activating mGluR2/3 could reduce the hyper-glutamatergic state associated with the disease (PubMed: 21532354). However, despite promising early results, the development was discontinued after the drug failed to demonstrate significant efficacy over placebo in late-stage clinical trials. The specific name provided, Gastrointestinal adsorption of LY2140023/LY404039 by aqueous activated charcoal, refers to a pharmacokinetic study (NCT00944112) evaluating the effect of an adsorbent on drug exposure rather than a biological target molecule.

Other names

mGluR2/3Metabotropic glutamate receptor 3GRM2GRM3mGlu2mGlu3

Agonist of mGluR2 and mGluR3 receptors