The potential of PDE4 inhibitors in respiratory disease.
Glucocorticosteroids remain the gold standard therapy for the prophylactic treatment of asthma. Concerns regarding its long-term use particularly in young children has provided an impetus for discovering novel anti-inflammatory molecules with high tolerability and clinical efficacy. Whilst for chronic obstructive pulmonary disease (COPD), there exist no pharmacological treatment for the prevention of decline in lung function. Targeting phosphodiesterase (PDE)4 is one example of this approach and inhibitors of this enzyme are the most advanced drug class in the respiratory pipeline. A number of potent PDE4 inhibitors have undergone clinical trials with moderate success. Tolerability and clinical efficacy issues have dampened enthusiasm in this area. However, with the prospect of newer potent and side effect free inhibitors on the horizon give this area guarded optimism. This review will summarise the most recent information concerning the effectiveness of PDE4 inhibitors as novel anti-inflammatory agents for the treatment of respiratory diseases.
Spina
Domenico
D
The Sackler Institute of Pulmonary Pharmacology, Hodgkin Building, GKT School of Biomedical Science, Kings College London, SE1 1UL, UK. domenico.spina@kcl.ac.uk
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D001993:Bronchodilator Agents / Q000494:pharmacology / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D006801:Humans; D007165:Immunosuppression Therapy; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology; D008171:Lung Diseases / Q000188:drug therapy* / Q000201:enzymology* / Q000503:physiopathology; D009130:Muscle, Smooth / Q000187:drug effects / Q000503:physiopathology; D010726:Phosphodiesterase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D020889:Rolipram / Q000494:pharmacology; D014839:Vomiting / Q000209:etiology
D000893:Anti-Inflammatory Agents; D001993:Bronchodilator Agents; D010726:Phosphodiesterase Inhibitors; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D020889:Rolipram