Non steroidal anti-inflammatory and anti-allergy agents.
Non steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used for inflammation therapy. The major drawback in using the NSAIDs is in their tendency to cause gastrointestinal toxicity. Since the roles of arachidonic acid (A.A) metabolites, as leukotrienes (Lts), prostaglandins (PGs) and thromboxanes (TXA(2)) as mediators of the inflammatory reaction were clarified, much effort has been made to develop inhibitors of the production of these chemical mediators as anti-inflammatory agents. These mediators also play important roles in some inflammatory or allergic diseases, acting either alone or in combination and inhibitors of 5-lipoxygenase (5-LOX) and/or cyclooxygenase isoforms 1,2 (COX-1,2) may be useful for the treatment of asthma, psoriasis and rheumatoid arthritis. Leukotrienes, the products of 5-LOX metabolism have been associated with immediate hypersensitivity reactions, anaphylaxis and asthma. In addition, active oxygen species (AOS) including superoxide anion (O(2)(-)), hydrogen peroxide, hydroxyl radical and ferric radical, mediate cell damage in a variety of pathophysiological conditions and are responsible for oxidative injury of enzymes, lipid membranes and DNA in living cells and tissues. Prostaglandins and leukotrienes in the arachidonate pathway linked with lipid peroxidation may amplify the oxidative damage. Nitric oxide (NO) plays also a role as an effector in inflammation, since PG and NO thought to be important in maintaining mucosal integrity. Dual or selective inhibitors, specific receptor antagonists, AOS scavengers, and NO donors have been under development for therapeutic application. Several classes of inhibitors have been identified and at least 12 major chemical series are known to affect PGs production directly. In this review, we account on our research work concerning NSAIDs combined with a reference of the recent literature.
Kontogiorgis
C A
CA
Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotelian University of Thessaloniki, Thessaloniki 54006, Greece.
Hadjipavlou-Litina
D J
DJ
D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy; D051545:Cyclooxygenase 1; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D015289:Leukotrienes / Q000502:physiology; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism
D018926:Anti-Allergic Agents; D018927:Anti-Asthmatic Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D015289:Leukotrienes; D008565:Membrane Proteins; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human; D011451:Prostaglandin-Endoperoxide Synthases