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. (c) 2006 Elsevier B.V. All rights reserved.