Dual phosphodiesterase PDE3/4 inhibitor Treatment of COPD Treatment of cystic fibrosis

Bronchospasm and inflammation are two fundamental targets in respiratory disorders. Therefore, it seems important to have bronchodilator and anti-inflammatory activity in a single molecule. Potentially dual inhibition of phosphodiesterase (PDE) 3 and PDE4 can not only induce more consistent bronchodilation than that induced by the inhibition of PDE3 or PDE4 alone, but also even reduce inflammation by suppressing the release of inflammatory mediators. Ensifentrine (RPL-554) is reported as a PDE3/4 inhibitor, although its affinity for PDE3 obtained from highly artificial experiments in a test tube is 3,440 times higher than that for PDE4. The clinical development of this molecule has shown that it is a fairly good bronchodilator capable of synergizing the effects of muscarinic antagonists. However, ensifentrine has not yet been compared with any of the dual bronchodilation fixeddose combinations currently available on the market, while there is currently no solid documentation of its ability to exert an anti-inflammatory action.