Biology Reference
In-Depth Information
Phosphodiesterase Inhibitors in the Treatment
of Inflammatory Diseases
C.P. Page and D. Spina
Contents
1 Introduction ...................................................................................... 392
2 Phosphodiesterase 4 ............................................................................. 393
3 Asthma and PDE4 ............................................................................... 394
4 COPD and PDE4 ................................................................................ 398
5 Other Inflammatory Diseases and PDE4 ...................................................... 401
6 Unwanted Side Effects . . . ...................................................................... 402
7 PDE4 Inhibition and the Future ................................................................ 405
8 Conclusion ....................................................................................... 406
References . . . .........................................................................................407
Abstract
Phosphodiesterase 4 (PDE4) belongs to a family of enzymes which
catalyzes the breakdown of 3, 5
0
-adenosine cyclic monophosphate (cAMP) and is
ubiquitously expressed in inflammatory cells. There is little evidence that inflam-
matory diseases are caused by increased expression of this isoenzyme, although
human inflammatory cell activity can be suppressed by selective PDE4 inhibitors.
Consequently, there is intense interest in the development of selective PDE4
inhibitors for the treatment of a range of inflammatory diseases, including asthma,
chronic obstructive pulmonary disease (COPD), inflammatory bowel disease, and
psoriasis. Recent clinical trials with roflumilast in COPD have confirmed the
therapeutic potential of targeting PDE4 and recently roflumilast has been approved
for marketing in Europe and the USA, although side effects such as gastrointestinal
disturbances, particularly nausea and emesis as well as headache and weight loss,
may limit the use of this drug class, at least when administered by the oral route.
However, a number of strategies are currently being pursued in attempts to improve
clinical efficacy and reduce side effects of PDE4 inhibitors, including delivery via
C.P. Page (
*
) and D. Spina
Sackler Institute of Pulmonary Pharmacology, Institute of Pharmaceutical Science, School
of Biomedical Sciences, King's College London, Franklin Wilkins Building, London SE1 9NH,
UK
e-mail: clive.page@kcl.ac.uk
