Chemogenetics is a powerful approach for selective activation of target receptors, in which the designed ligand can be applied non-invasively to live animals. Indeed, DREADD, one of the chemogenetic methods used widely in the neuroscience field, is regarded as a complementary method to optogenetics. For most current chemogenetic approaches, mutations are introduced into the ligand-binding domain, and the mutated receptors (i.e., designer receptors) are selectively activated by the designed ligands. Although powerful for selective regulation of downstream signals of the target receptor, native ligand-binding properties of the receptors are affected or lost. Consequently, it is challenging to apply conventional chemogenetics to understand the physiological roles of endogenous receptors. In this direction, we have recently developed a chemogenetic method, dA-CBC (direct-activation via coordination-based chemogenetics), for selective activation of mGlu1, a metabotropic glutamate receptor subtype. dA-CBC is a unique chemogenetic approach in which histidine mutations are introduced into an appropriate position of the target GPCR based on structural information about the receptor. A designed palladium complex induces a structural change to the GPCR for receptor activation, which allowed chemogenetic regulation of mGlu1 endogenously expressed in mice. In this talk, I will present the recent progress of our GPCR chemogenetics.