title: Selective PDE inhibitors as novel treatments for respiratory diseases.
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.
authors.affiliation: 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
authors.forename: Clive P
authors.initials: CP
authors.lastname: Page
authors.forename: Domenico
authors.initials: D
authors.lastname: Spina
mesh_terms: D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D004359:Drug Therapy, Combination / Q000009:adverse effects; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D058990:Molecular Targeted Therapy / Q000009:adverse effects; D058987:Phosphodiesterase 3 Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D058988:Phosphodiesterase 4 Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D010726:Phosphodiesterase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D010727:Phosphoric Diester Hydrolases / Q000737:chemistry / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D012137:Respiratory System / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism
chemical_list: D007527:Isoenzymes; D058987:Phosphodiesterase 3 Inhibitors; D058988:Phosphodiesterase 4 Inhibitors; D010726:Phosphodiesterase Inhibitors; D010727:Phosphoric Diester Hydrolases