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

Theophylline is commonly used in the treatment of obstructive airway diseas es. The identification and functional characterization of different phospho diesterase (PDE) isoenzymes has led to the development of various isoenzyme -selective inhibitors as potential anti-asthma drugs. Considering the distr ibution of isoenzymes in target tissues, with high activity of PDE3 and PDE 4 in airway smooth muscle and inflammatory cells, selective inhibitors of t hese isoenzymes may add to the therapy of chronic airflow obstruction. Howe ver, initial data from clinical trials with selective PDE3 and PDE4 inhibit ors have been somewhat disappointing and have tempered the expectations con siderably since these drugs had limited efficacy and their use was clinical ly limited through side effects. The improved understanding of the molecula r biology of PDEs enabled the synthesis of novel drugs with an improved ris k/benefit ratio. These 'second generation' selective drugs have produced mo re promising clinical results not only for the treatment of bronchial asthm a but also for the treatment of chronic obstructive pulmonary disease.