6533b831fe1ef96bd1298e7c
RESEARCH PRODUCT
PDE4 inhibitors as new anti-inflammatory drugs: effects on cell trafficking and cell adhesion molecules expression.
Esteban J. MorcilloMaria-jesus SanzJulio CortijoJulio Cortijosubject
CyclopropanesChemokineCyclohexanecarboxylic Acidsmedicine.drug_classPhosphodiesterase Inhibitorsmedicine.medical_treatmentAnti-Inflammatory AgentsCarboxylic AcidsAminopyridinesInflammationPharmacologyAnti-inflammatoryPulmonary Disease Chronic ObstructiveIn vivoCell MovementNitrilesmedicineHumansPharmacology (medical)RoflumilastPharmacologybiologyCell adhesion moleculeChemistryCilomilastCyclic Nucleotide Phosphodiesterases Type 4Cytokine3'5'-Cyclic-AMP PhosphodiesterasesImmunologyBenzamidesbiology.proteinmedicine.symptomCell Adhesion Moleculesmedicine.drugdescription
Phosphodiesterase 4 (PDE4) is a major cyclic AMP-hydrolyzing enzyme in inflammatory and immunomodulatory cells. The wide range of inflammatory mechanisms under control by PDE4 points to this isoenzyme as an attractive target for new anti-inflammatory drugs. Selective inhibitors of PDE4 have demonstrated a broad spectrum of anti-inflammatory activities including the inhibition of cellular trafficking and microvascular leakage, cytokine and chemokine release from inflammatory cells, reactive oxygen species production, and cell adhesion molecule expression in a variety of in vitro and in vivo experimental models. The initially detected side effects, mainly nausea and emesis, appear at least partially overcome by the 'second generation' PDE4 inhibitors, some of which like roflumilast and cilomilast are in the later stages of clinical development for treatment of chronic obstructive pulmonary disease. These new drugs may also offer opportunities for treatment of other inflammatory diseases.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2004-12-15 | Pharmacologytherapeutics |