title: [Pharmacological profile of roflumilast].
abstract: Roflumilast (3-cyclopropylmethoxy-4-difluoromethoxy-n-(3,5-dichloropyrid-4-yl)benzamide) was the first agent of a novel pharmacological class, selective phosphodiesterase 4 (PDE(4)) inhibitors, approved for the use of chronic obstructive pulmonary disease (COPD). The molecular mechanism of action of roflumilast is inhibition of the PDE(4) isoenzyme with a consequent increase of cyclic adenosine monophosphate. Roflumilast evidently has several pharmacological effects: antiinflammatory, anti-emphysema, and antibiotic actions. This drug also inhibits pulmonary hypertension and reduces mucus hypersecretion. The pharmacological actions leading to these effects are: a) inhibition of reactive oxygen species formation in epithelial cells, neutrophils and smooth muscle cells; b) inhibition of smooth muscle cell proliferation in the pulmonary artery, endothelial cells and probably some inflammatory cells causing pulmonary vascular remodeling; c) inhibition of fibroblasts, with a consequent reduction in pulmonary remodeling and, finally, d) inhibition of mucus production and improved ciliary beat frequency. In summary, roflumilast is the first non-steroidal anti-inflammatory drug that can be used in the treatment of COPD.
authors.affiliation: Unidad de Docencia e Investigación, Consorcio Hospital General Universitario de Valencia, España. cortijo_jul@gva.es
authors.forename: Julio
authors.initials: J
authors.lastname: Cortijo Gimeno
authors.forename: Esteban
authors.initials: E
authors.lastname: Morcillo Sánchez
mesh_terms: D056151:Airway Remodeling / Q000187:drug effects; D000631:Aminopyridines / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D001549:Benzamides / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D002923:Cilia / Q000187:drug effects; D003521:Cyclopropanes / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D015394:Molecular Structure; D009093:Mucus / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects; D016877:Oxidants / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects; D058988:Phosphodiesterase 4 Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy; D011656:Pulmonary Emphysema / Q000188:drug therapy; D051381:Rats; D012906:Smoke / Q000009:adverse effects; D014026:Nicotiana
chemical_list: D000631:Aminopyridines; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001549:Benzamides; D003521:Cyclopropanes; D016877:Oxidants; D058988:Phosphodiesterase 4 Inhibitors; D012906:Smoke; C424423:Roflumilast