Selective PDE inhibitors as novel treatments for respiratory diseases

Clive P Page; Domenico Spina

doi:10.1016/j.coph.2012.02.016

Selective PDE inhibitors as novel treatments for respiratory diseases

Curr Opin Pharmacol. 2012 Jun;12(3):275-86. doi: 10.1016/j.coph.2012.02.016. Epub 2012 Apr 11.

Authors

Clive P Page¹, Domenico Spina

Affiliation

¹ Sackler Institute of Pulmonary Pharmacology, Institute of Pharmaceutical Science, Franklin Wilkins Building, King's College London, London SE1 9NH, UK. clive.page@kcl.ac.uk

PMID: 22497841
DOI: 10.1016/j.coph.2012.02.016

Abstract

Phosphodiesterases (PDEs) are a family of enzymes which catalyse the metabolism of the intracellular cyclic nucleotides, c-AMP and c-GMP that are expressed in a variety of cell types and in the context of respiratory diseases, It is now recognised that the use of PDE3, PDE4 and mixed PDE3/4 inhibitors can provide clinical benefit to patients with asthma or chronic obstructive pulmonary disease (COPD). The orally active PDE4 inhibitor Roflumilast-n-oxide has been approved for treatment of severe exacerbations of COPD as add-on therapy to standard drugs. This review discusses the involvement of PDEs in airway diseases and various strategies that are currently being pursued to improve efficacy and reduce side-effects of PDE4 inhibitors, including delivery via the inhaled route, mixed PDE inhibitors and/or antisense biologicals targeted towards PDE4.

Publication types

Review

MeSH terms

Animals
Asthma / drug therapy*
Asthma / enzymology
Asthma / metabolism
Drug Therapy, Combination / adverse effects
Humans
Isoenzymes / antagonists & inhibitors
Molecular Targeted Therapy* / adverse effects
Phosphodiesterase 3 Inhibitors / adverse effects
Phosphodiesterase 3 Inhibitors / pharmacology
Phosphodiesterase 3 Inhibitors / therapeutic use
Phosphodiesterase 4 Inhibitors / adverse effects
Phosphodiesterase 4 Inhibitors / pharmacology
Phosphodiesterase 4 Inhibitors / therapeutic use
Phosphodiesterase Inhibitors / adverse effects
Phosphodiesterase Inhibitors / pharmacology
Phosphodiesterase Inhibitors / therapeutic use*
Phosphoric Diester Hydrolases / chemistry
Phosphoric Diester Hydrolases / metabolism
Pulmonary Disease, Chronic Obstructive / drug therapy*
Pulmonary Disease, Chronic Obstructive / enzymology
Pulmonary Disease, Chronic Obstructive / metabolism
Respiratory System / drug effects*
Respiratory System / enzymology
Respiratory System / metabolism

Substances

Isoenzymes
Phosphodiesterase 3 Inhibitors
Phosphodiesterase 4 Inhibitors
Phosphodiesterase Inhibitors
Phosphoric Diester Hydrolases