Nonsteroidal antiinflammatory drugs inhibiting prostanoid efflux: As easy as ABC?

摘要

Nonsteroidal antiinflammatory drugs (NSAIDs) and prosta-noids continue to be fascinating research targets. Humans have been using NSAIDs in one form or another, from folk remedies through to the products of modern pharmaceutical research, for thousands of years. However, we still have not characterized all of the systems through which these drugs produce their beneficial and harmful effects (1, 2). We are certain, from seminal work carried out in the 1960s and early 1970s, that NSAIDs have the common property of inhibiting the activity of cyclooxygenase (COX), the enzyme that initiates the formation of prostanoids (1). An explosion of research in the last decade or so has led us to understand that COX exists in two forms, COX-1 and -2, and that drugs targeted against COX-2 still retain the antiinflammatory properties of traditional NSAIDs (1, 2). Because the traditional NSAIDs generally inhibit both isoforms of COX, it is the ability of NSAIDs to inhibit COX-1 that has become associated with their deleterious side effects, particularly within the gastrointestinal tract.