The metabotropic glutamate receptor 4 (mGluR4) belongs to the Group III mGluRs (Class C G Protein-Coupled Receptors) and is negatively coupled to adenylate cyclase via activation of the Gαi/o protein. It is expressed primarily on presynaptic terminals, functioning as an autoreceptor or heteroceptor and its activation thus leading to decreases in glutamate and GABA transmitter release into the synapse.
mGluR4 PAM is emerging as a promising target for the treatment of motor (and non-motor) symptoms as well as a disease-modifying agent in Parkinson’s disease through a non-dopaminergic approach.
Addex has identified several new series of compounds acting as mGlu4 positive allosteric modulators with nanomolar potency, completely selective versus all other mGluRs, and achieving brain penetration compatible with a treatment for CNS disorders. The program is in late stage lead optimisation.
ADX88178 has been published as pharmacological tool to explore the potential of the mGlu4 PAM approach, but also to better understand the function of this receptor (see Publications section).