Selective phosphodiesterase inhibitors for the treatment of bronchial asthma and chronic obstructive pulmonary disease.

Theophylline is commonly used in the treatment of obstructive airway diseases. The identification and functional characterization of different phosphodiesterase (PDE) isoenzymes has led to the development of various isoenzyme-selective inhibitors as potential anti-asthma drugs. Considering the distribution of isoenzymes in target tissues, with high activity of PDE3 and PDE4 in airway smooth muscle and inflammatory cells, selective inhibitors of these isoenzymes may add to the therapy of chronic airflow obstruction. However, initial data from clinical trials with selective PDE3 and PDE4 inhibitors have been somewhat disappointing and have tempered the expectations considerably since these drugs had limited efficacy and their use was clinically limited through side effects. The improved understanding of the molecular biology of PDEs enabled the synthesis of novel drugs with an improved risk/benefit ratio. These 'second generation' selective drugs have produced more promising clinical results not only for the treatment of bronchial asthma but also for the treatment of chronic obstructive pulmonary disease.