Abstract
This chapter describes the various aspects of phosphodiesterase 4 (PDE4) inhibitors. PDE4 is the predominant isozyme present in inflammatory cells and selective PDE4 inhibitors are a popular target for novel anti-inflammatory drugs. The distribution of PDE4 in inflammatory cells and airway smooth muscle, and the effects of selective PDE4 inhibitors in vitro , has been reviewed. In Phase II trials, Cilomilast showed efficacy in exercise-induced asthma and a dose of 15 mg has been reported to improve respiratory function in patients with asthma who are not adequately controlled by inhaled corticosteroids. Treatment with Cilomilast for 6 weeks resulted in a 160 ml improvement in trough forced expiratory volume (FEV) when compared to placebo. A large number of structurally diverse, selective PDE4 inhibitors have demonstrated their ability to inhibit bronchoconstriction and airway hyper-responsiveness, eosinophil infiltration and local cytokine recruitment in a variety of models involving a range of stimuli. Efficacy has been shown in mice, rats, guinea pigs, dogs, and monkeys, and the therapeutic potential of PDE4 inhibitors in asthma, allergic rhinitis, and chronic obstructive pulmonary disease (COPD) has been extensively reviewed.
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