FDA Drug Repurposing Uncovers Modulators of Dopamine D₂ Receptor Localization via Disruption of the NCS-1 Interaction.

ABSTRACT: Dopamine D₂ receptor (D₂R) regulates key aspects of motor control, cognition, and reward. Its function depends not only on ligand binding and signaling efficacy but also on the dynamic control of receptor localization at the cell surface. Neuronal calcium sensor 1 (NCS-1) interacts with D₂R in a Ca²⁺-dependent manner. Using in vitro and cellular assays, we found that NCS-1 promotes D₂R trafficking to the plasma membrane through active exocytosis while preserving canonical receptor pharmacology. A screen of FDA-approved drugs identified protein-protein interaction (PPI) modulators targeting the NCS-1/D₂R interface. Azilsartan medoxomil, atorvastatin, and vilazodone disrupt this interaction, reducing D₂R surface exp

SUBMITTER: Munoz-Reyes D 

PROVIDER: S-EPMC12670427 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature