Research Projects

Dopamine D2 receptor (D2R) is a key neuromodulator that regulates various central nervous system functions through G protein and β-arrestin-dependent signaling pathways. Any disruption in D2R signaling can lead to neuropathological conditions like schizophrenia and Parkinson's disease. Conventional antipsychotic drugs act as potent D2R blockers, but the biased ligand/drug that selectively modulates undesired function without affecting other physiological functions has not been described. The researchers hypothesize that biased ligands mediate D2R receptor activation distinct from native or balanced ligands, allowing selective signaling functions via coupling to either G-protein or β-arrestin. They propose high-throughput screening of biased ligands for D2R with varying affinity and efficacy, using ligand binding and effector coupling assays. This study aims to unravel the current conceptual framework of biased signaling and D2R receptor pharmacology.