The metabotropic receptor mGluR2 belongs to the class C G Protein-Coupled Receptor family (group II mGluRs). This receptor shows a broad distribution throughout the cortex as well as high expression in the hippocampus and perforant path. Importantly, activation of mGluR2 leads to inhibition of glutamate release in the synapse. In this respect, Addex believes that inhibition of mGluR2 with a selective negative allosteric modulator (NAM) may be of therapeutic use to treat medical conditions which may be linked to low glutamate levels in the brain.
Addex is currently optimizing multiple chemical series of mGluR2 NAMs offering advanced compounds at the late stage of lead optimization. Representative compounds of our series have demonstrated effect in memory impairment model in rodents mimicking aspects of pathophysiology and progressive memory impairment observed in Alzheimer’s disease.
Although other drugs targeting mGluR2 are in development none are known to be as exquisitely selective for mGluR2 over other mGlu receptors (1-8) as the Addex molecules. As a result, Addex is developing the most advanced subtype selective mGluR2 NAM, a differentiating factor that may confer significant advantages in terms of efficacy and safety in later testing.