Year: 2026
Type: preprint
Abstract: The dopamine D 2 receptor is a principal target of antipsychotic and antiparkinsonian drugs, yet well-characterized fluorescent ligands for the D 2 receptor remain scarce compared with its relative, the D 3 receptor. Here we show that fluorescent ligands developed for the D 3 subtype can be repurposed as tools for studying the D 2 receptor pharmacology. Using a machine-learning-assisted, live-cell fluorescence microscopy assay, we screened twelve fluorescent probes and identified eight ligands that bound specifically to the D 2 receptor at 10 nM. Four ligands exhibited classical saturable binding, yielding K d in the nanomolar range, whereas the remaining probes displayed unsaturated, time-dependent binding profiles. Kinetic analyses revealed substantial differences in association and dissociation behavior, highlighting the importance of time-resolved measurements. Competition binding with dopamine and haloperidol yielded affinity estimates consistent with literature values. These results expand the toolkit of validated D 2 receptor fluorescent probes and support cross-receptor repurposing as a strategy for fluorescent ligand development. Abstract Figure
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funder: Eesti Teadusagentuur
OpenAlex ID: W7221083403