Inverse agonism at beta-adrenergic receptors: therapeutic implications

Ligands for G-protein-coupled receptors constitute important means in therapeutic applications. Therefore, developing new ligands for these receptors has been one of the major therapeutic aim. In classical pharmacology, ligands for G-protein coupled receptors were classified as agonist, partial agonist and antagonist. Under this classification, it was believed that three different choices of ligands are available in the treatment of diseases or in the strategies to develop new drugs. Recently this classification has been extended to include a spectrum of (full) agonist, partial agonist, neutral antagonist, partial inverse agonist and (full) inverse agonist. The new classification has brought new perspectives in the understanding of pathophysiology, in the strategies of developing new drugs and in the treatment of diseases. Now the challenge is to figure out the appropriate choice of ligand for the treatment of relevant diseases. Inverse agonists became particularly interesting with the understanding that G-protein coupled receptors may have spontaneous activity that can be inhibited by these ligands. In this review, developments in the concept of inverse agonism at G-protein-coupled receptors and beta-adrenergic receptors and therapeutic implications of inverse agonists are discussed.