Dopamine D3 receptor ligands: recent advances in the control of subtype selectivity and intrinsic activity

Various pharmacological studies have implicated the dopamine D(3) receptor as an interesting therapeutic target in the treatment of different neurological disorders. Because of these putative therapeutic applications, D(3) receptor ligands with diverse intrinsic activities have been an active field of research in recent years. Separation of purely D(3)-mediated drug effects from effects produced by interactions with similar biogenic amine receptors allows to verify the therapeutic impact of D(3) receptors and to reduce possible side-effects caused by "promiscuous" receptor interactions. The requirement to gain control of receptor selectivity and in particular subtype selectivity has been a challenging task in rational drug discovery for quite a few years. In this review, recently developed structural classes of D(3) ligands are discussed, which cover a broad spectrum of intrinsic activities and show interesting selectivities.