The mGluR7 receptor is the most highly conserved of all mGluR subtypes across mammalian species exhibiting the widest distribution in the brain among mGluRs.
It is localized presynaptically at a broad range of glutamatergic and GABAergic synapses and has been postulated to be one of the most important mGluR subtypes in regulating CNS function.
Studies in a number of behavioural models have shown that mGluR7 knockout animals exhibit reduced anxiety- and depression-like responses in a variety of stress-related paradigms and deficits in amygdala-dependent behaviours (fear response and conditioned taste aversion. These data are consistent with the abundant localization of mGluR7 in brain regions involved in the control of fear and emotion.
Our mGluR7 negative allosteric modulator (NAM) program is currently in lead optimization phase where compounds representing multiple chemical series have been shown to be efficacious in animal models of anxiety. Profiling of this compound in preclinical rodent models shows that there are no significant side-effects in body temperature or motor coordination.