The mGlu7 receptor is the most highly conserved of all metabotropic glutamate receptor subtypes across mammalian species exhibiting the widest distribution in the brain among mGluRs. It is localized in the presynaptic active zone and abundantly expressed in brain regions such as neocortex, hippocampus, amygdala, locus coeruleus, thalamus and hypothalamus, structures involved in the control of fear and emotion. mGlu7 is expressed both at glutamatergic and GABAergic synapses and has been postulated to be one of the most important mGlu receptor subtypes in regulating CNS function.
Behavioural studies have shown that mGlu7 knockout animals exhibit reduced anxiety- and depression-like responses in a variety of stress-related paradigms and deficits in amygdala-dependent behaviours. mGlu7 receptor inhibition appears as a novel and well differentiated approach for the treatment of anxiety and stress-related disorders. In addition, the expression of mGlu7 receptor in the inner ear suggests its modulation could represent a potential treatment of hearing disorders such as age-related hearing impairment and tinnitus.
mGlu7 negative allosteric modulator (NAM) series were identified from our corporate library of small molecules using our proprietary biological tools, and are being progressed though late lead optimisation to reach clinical candidate phase.