Xanthines like
theophylline have long been recognised as being effective drugs for the treatment of
asthma and
chronic obstructive pulmonary disease (
COPD). They are of interest as they possess both anti-inflammatory and
bronchodilator activity in the same molecule. Since the discovery of
phosphodiesterases (
PDEs) in the late 1950s, it has been suggested that
xanthines work, in part, by acting as non-selective PDE inhibitors. However, it has also been suggested that the ability of
xanthines to non-selectively inhibit
PDEs contributes to their many unwanted side effects, thus limiting their use since the arrival of inhaled drugs with more favourable safety profiles. As our understanding of
PDEs has improved over the last 30 years, and with the recognition that the distribution of different
PDEs varies across different cell types, this family of
enzymes has been widely investigated as targets for novel drugs. In particular, PDE3 in airway smooth muscle and PDE4 and PDE7 in inflammatory cells have been targeted to provide new
bronchodilators and
anti-inflammatory agents, respectively. This review discusses the progress made in this field over the last decade in the development of selective PDE inhibitors to treat
COPD and
asthma.