Multivalent approaches and beyond: novel tools for the investigation of dopamine D₂ receptor pharmacology

The dopamine D₂ receptor (D₂R) has been implicated in the symptomology of disorders such as schizophrenia and Parkinson's disease. Multivalent ligands provide useful tools to investigate emerging concepts of G protein-coupled receptor drug action such as allostery, bitopic binding and receptor dimerization. This review focuses on the approaches taken toward the development of multivalent ligands for the D₂R recently and highlights the challenges associated with each approach, their utility in probing D₂R function and approaches to develop new D₂R-targeting drugs. Furthermore, we extend our discussion to the possibility of designing multitarget ligands. The insights gained from such studies may provide the basis for improved therapeutic targeting of the D₂R.