Orphan seven transmembrane domain receptors: reversing pharmacology

The application of molecular genetic approaches to the study of seven transmembrane domain receptors has allowed the cloning of many receptors for which the ligand is initially unknown. These are commonly referred to as 'orphan receptors', and several have subsequently proved to be important pharmacological targets. This article discusses how these receptor sequences were isolated, and presents some of the methods by which the corresponding ligands were identified. These examples are used to propose a rational approach for the study of further orphan receptors.