Background: Non-steroidal anti-inflammatory drugs are the oldest and most widely
used medicines. However, their untoward effects, especially gastrointestinal toxicity, remain the
main obstacle to their application. Because of their mechanism of action, cycloxygenase (COX)
inhibition, in combination with the weekly acidic character of most of them, major protective
mechanisms of the gastrointestinal system are suppressed and deregulated.
Objective: In this review, several compounds designed to retain anti-inflammatory activity, but
devoid of gastrointestinal side effects, are presented. Thus, gastro-protective drugs, selective
COX-2 inhibitors, nitric monoxide- and hydrogen sulphide-releasing agents, prodrugs, lipoxygenase
(LOX) inhibitors and dual COX/LOX inhibitors are presented. Their mechanism of action,
as well as their advantages and disadvantages are discussed.
Conclusion: Efforts, aiming to the development of safe non-steroidal anti-inflammatory agents,
are evolving, however there are still several problems concerning gastro-protection to be efficiently
solved, thus, design of effective and safe agents for the treatment of inflammatory conditions
still remains a major challenge.