The
prostaglandin series of bioactive compounds is formed by the interaction of two distinct but related
enzymes, cyclo-oxygenase-1 (COX-1) and
cyclooxygenase-2 (COX-2). COX-1 is a constitutive form which is present mainly in the gastric mucosa, kidney and platelets. COX-2 is mainly an inducible form, although also to some extent present constitutively in the CNS, the juxtaglomerular apparatus of the kidney and in the placenta during late gestation. Both
isoforms contribute to the inflammatory process, but COX-2 is of considerable therapeutic interest as it is induced, resulting in an enhanced formation of
prostaglandins, during acute as well as chronic
inflammation. Conventional
NSAIDs inhibit both
isoforms to a similar extent and in an approximately equal dose and concentration range. The two recently developed and clinically available selective
COX-2 inhibitors,
celecoxib and
rofecoxib, are about 100-1000 times more selective on the COX-2 than on the COX-1
isoform. In Europe
rofecoxib is today indicated for the symptoms and signs of
osteoarthritis, whereas
celecoxib is indicated for both
osteoarthritis and
rheumatoid arthritis. The major clinical interest of these drugs has been related to the lower incidence of gastrointestinal
bleeding which, with the conventional COX-1/COX-2 agents has been a source of hospitalisation, disablement and death, especially in the elderly. Clinical trials have convincingly demonstrated that
celecoxib and
rofecoxib in clinical use induce very few gastrointestinal complications compared to conventional and non-selective
NSAIDs. However, the well known
contraindications for
NSAIDs, such as late pregnancy,
aspirin-induced asthma,
congestive heart failure and renal dysfunction, will so far apply also to the
COX-2 inhibitors. Compared to the traditional and non-selective
NSAIDs,
COX-2 inhibitors may provide an insight into additional therapeutic areas, such as
gastrointestinal cancer and
dementia, where the potential relevance to COX-2 mechanisms are currently being explored and clinical trials being performed. With the rapid clinical acceptance of
celecoxib and
rofecoxib, knowledge about their clinical usefulness in various inflammatory disease states and
pain disorders is increasing. For the many patients suffering from such conditions, the selective
COX-2 inhibitors are likely to become a significant addition to the therapeutic arsenal of
analgesic and anti-inflammatory drugs.