SELECTIVE PHOSPHODIESTERASE INHIBITORS IN THE THERAPY OF ASTHMA

Cyclic nucleotide phosphodiesterases form a group of enzymes that cata lyse the breakdown of the intracellular second messengers cyclic AMP a nd cyclic GMP. Inhibitors of these enzymes, such as theophylline and e nprofylline, are standard agents in the therapy of bronchial asthma bu t are limited in their usefulness by their poor potency and frequent a dverse effects. An extensive research effort in recent years has ident ified 7 families of phosphodiesterase, comprising more than 33 separat e isoenzymes, that may represent targets for novel anti-asthma therapi es. The role of cyclic AMP and cyclic GMP in the regulation of cell fu nction in many airway tissues and immune cells involved in the pathoph ysiology of asthma has been identified, and the pharmacological action s of isoenzyme-selective phosphodiesterase inhibitors upon these cells are under investigation. Although the first target for investigation was the airway smooth muscle, whose episodic constriction is the prima ry sign of asthma, increasing interest is developing in the ability of phosphodiesterase inhibitors to modulate the activity of inflammatory cells and, thereby, to modify the underlying pathological processes o f the disease. Recent advances in the understanding of the actions of phosphodiesterase inhibitors on T lymphocytes and eosinophils are part icularly exciting, and may indicate a place for these drugs in a new g eneration of treatments for asthma.