1: Trends Pharmacol Sci. 2007 Aug;28(8):438-46. Epub 2007 Jul 13. Versatility of GPCR recognition by drugs: from biological implications to therapeutic relevance. Bosier B, Hermans E. Unité de Chimie Pharmaceutique et de Radiopharmacie (UCL 7340), Université Catholique de Louvain, B-1200 Brussels, Belgium. Most drugs acting on G-protein-coupled receptors (GPCRs) are classically defined as agonists, partial agonists or antagonists. This simplified classification seems sufficient to explain most of their therapeutic properties. The more recent description of inverse agonism has helped to revise theoretical models of GPCR function, but the therapeutic implications of the new concepts remain clearly restricted. Further complexity has arisen with demonstrations that a given receptor can adopt various conformations that support coupling with distinct G proteins. Because the related signaling pathways seem to be differentially affected by some ligands, the concept of 'functional selectivity' has been proposed, calling for a revision of the definitions of agonism and intrinsic efficacy. Evidence of complexity in G-protein coupling and examples of functional selectivity are accumulating, opening perspectives for drug development. Although such complexity should be regarded as an opportunity to gain pharmacological specificity, unraveling the physiological implications of these concepts is essential before their therapeutic relevance can be defined. PMID: 17629964 [PubMed - indexed for MEDLINE] Related Links The evasive nature of drug efficacy: implications for drug discovery. [Trends Pharmacol Sci. 2007] PMID:17659355 GPCR functional selectivity has therapeutic impact. [Trends Pharmacol Sci. 2007] PMID:17629962 G protein-coupled receptors: a count of 1001 conformations. [Fundam Clin Pharmacol. 2005] PMID:15660959 New concepts in drug discovery: collateral efficacy and permissive antagonism. [Nat Rev Drug Discov. 2005] PMID:16264435 Collateral efficacy in drug discovery: taking advantage of the good (allosteric) nature of 7TM receptors. [Trends Pharmacol Sci. 2007] PMID:17629960