Life after PDE4: overcoming adverse events with dual-specificity phosphodiesterase inhibitors.

Despite reports of the efficacy of phosphodiesterase 4 (PDE4) inhibitors in some Phase III clinical trials of asthma and chronic obstructive pulmonary disease, the presence of dose-limiting side effects continue to hamper their development. Consequently, new approaches are required to improve the therapeutic ratio and the safety of these compounds. One option might lie in the synthesis of small molecules with a broader PDE specificity. The development of dual-specificity compounds that inhibit PDE4 and PDE1, PDE3, PDE5 or PDE7 could be beneficial for the treatment of chronic inflammatory lung diseases and are currently being investigated.