Therapeutic benefit of PDE4 inhibitors in inflammatory diseases.
Intracellular levels of cyclic nuclec tides are closely regulated by distinct families of PD Es, which are responsible for the breakdown and degradation of cyclic nucleotides within cells. Type 4 PDEs have the potency to modulate the release of inflammatory mediators through cAMP-dependent and -independent mechanisms. Selective targeting of PDE4 is currently being investigated as a novel therapeutic approach in the treatment of inflammation-associated respiratory diseases such as asthma and COPD. The development of several PDE4 inhibitors, including roflumilast and cilomilast, reflects the success of this approach. In principle, therapeutic intervention of an inflammatory response by PDE4 inhibitors may be extended to other chronic inflammatory disease states such as psoriasis, rheumatoid arthritis and inflammatory bowel diseases (e.g., Crohns disease and ulcerative colitis). This retiiew explores the feasibility of PDE4 inhibitors as a promising alternative for therapeutic intervention in systemic inflammation and inflammation-based disease.
Dastidar
Sunanda G
SG
Ranbaxy Research Laboratories, Department of Pharmacology, New Drug Discovery Research, Gurgaon 122 001, India. sunanda.dastidar@ranbaxy.com
Rajagopal
Deepa
D
Ray
Abhijit
A
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001168:Arthritis / Q000188:drug therapy; D001249:Asthma / Q000188:drug therapy; D000242:Cyclic AMP / Q000378:metabolism; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D003876:Dermatitis, Atopic / Q000188:drug therapy; D015507:Drugs, Investigational / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000201:enzymology; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011565:Psoriasis / Q000188:drug therapy; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy; D015398:Signal Transduction / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D015507:Drugs, Investigational; D010726:Phosphodiesterase Inhibitors; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4