SELECTIVE PHOSPHODIESTERASE INHIBITORS IN THE THERAPY OF ASTHMA

Cyclic nucleotide phosphodiesterases form a group of enzymes that catalyse the breakdown of the intracellular second messengers cyclic AMP and cyclic GMP. Inhibitors of these enzymes, such as theophylline and enprofylline, are standard agents in the therapy of bronchial asthma but are limited in their usefulness by their poor potency and frequent adverse effects. An extensive research effort in recent years has identified 7 families of phosphodiesterase, comprising more than 33 separate isoenzymes, that may represent targets for novel anti-asthma therapies. The role of cyclic AMP and cyclic GMP in the regulation of cell function in many airway tissues and immune cells involved in the pathophysiology of asthma has been identified, and the pharmacological actions 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 primary 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 of the disease. Recent advances in the understanding of the actions of phosphodiesterase inhibitors on T lymphocytes and eosinophils are particularly exciting, and may indicate a place for these drugs in a new generation of treatments for asthma.