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]

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