Phosphodiesterases As Therapeutic Targets for Respiratory Diseases

Publication date: Available online 10 February 2019Source: Pharmacology & TherapeuticsAuthor(s): Haoxiao Zuo, Isabella Cattani-Cavalieri, Nshunge Musheshe, Viacheslav O. Nikolaev, Martina SchmidtAbstractChronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD) and asthma, affect millions of people all over the world. Cyclic adenosine monophosphate (cAMP) which is one of the most important second messengers, plays a vital role in relaxing airway smooth muscles and suppressing inflammation. Given its vast role in regulating intracellular responses, cAMP provides an attractive pharmaceutical target in the treatment of chronic respiratory diseases. Phosphodiesterases (PDEs) are enzymes that hydrolyze cyclic nucleotides and help control cyclic nucleotide signals in a compartmentalized manner. Currently, the selective PDE4 inhibitor, roflumilast, is used as an add-on treatment for patients with severe COPD associated with bronchitis and a history of frequent exacerbations. In addition, other novel PDE inhibitors are in different phases of clinical trials. The current review provides an overview of the regulation of various PDEs and the potential application of selective PDE inhibitors in the treatment of COPD and asthma. The possibility to combine various PDE inhibitors as a way to increase their therapeutic effectiveness is also emphasized.
Source: Pharmacology and Therapeutics - Category: Drugs & Pharmacology Source Type: research