The search for selective inhibitors of PDE4 as novel anti-inflammatory drugs has continued for more than 30 years. Although several compounds have demonstrated
therapeutic effects in diseases such as
asthma,
COPD,
atopic dermatitis and
psoriasis, none have reached the market. A persistent challenge in the development of
PDE4 inhibitors has been
drug-induced gastrointestinal adverse effects, such as
nausea. However, extensive clinical trials with well-tolerated doses of
roflumilast (Daxas; Nycomed/Mitsubishi Tanabe Pharma Corp/Forest Laboratories Inc) in
COPD, a disease that is generally unresponsive to existing
therapies, have demonstrated significant therapeutic improvements. In addition, GlaxoSmithKline plc is developing 256066, an inhaled formulation of a
PDE4 inhibitor that has demonstrated efficacy in trials in
asthma, and
apremilast from Celgene Corp has been reported to be effective for the treatment of
psoriasis. Despite the challenges and complications that have been encountered during the development of
PDE4 inhibitors, these drugs may provide a genuinely novel class of
anti-inflammatory agents, and there are several compounds in development that could fulfill that promise.