The metabolic effects of inhibitors of 5-lipoxygenase and of cyclooxygenase 1 and 2 are an advancement in the efficacy and safety of anti-inflammatory therapy

Celotti, 2001, Anti-inflammatory drugs: new multitarget compounds to face an old problem. The dual inhibitor concept, Pharmacol. Res., 43, 429, 10.1006/phrs.2000.0784 Turini, 2002, Cyclooxygenase-2: a therapeutic target, Annu. Rev. Med., 53, 35, 10.1146/annurev.med.53.082901.103952 Funk, 2001, Prostaglandins and leukotrienes: advances in eicosanoid biology, Science, 4, 1871, 10.1126/science.294.5548.1871 Hinz, 2002, Cyclooxygenase 2–10 years later, J. Pharmacol. Exp. Ther., 300, 367, 10.1124/jpet.300.2.367 Peskar, 2001, Role of cyclooxygenase-2 in gastric mucosal defense, Life Sci., 69, 2993, 10.1016/S0024-3205(01)01407-2 Mizuno, 1997, Induction of cyclooxygenase-2 in gastric mucosal lesions and its inhibition by the specific antagonist delays healing in mice, Gastroenterology, 112, 387, 10.1053/gast.1997.v112.pm9024292 Halter, 2001, Cyclooxygenase 2-implications on maintenance of gastric mucosal integrity and ulcer healing: controversial issues and perspectives, Gut, 49, 443, 10.1136/gut.49.3.443 Mukherjee, 2002, Selective cyclooxygenase-2 (COX-2) inhibitors and potential risk of cardiovascular events, Biochem. Pharmacol., 63, 817, 10.1016/S0006-2952(02)00842-0 Bolli, 2002, Discovery of a new function of cyclooxygenase (COX)-2: COX-2 is a cardioprotective protein that alleviates ischemia/reperfusion injury and mediates the late phase of preconditioning, Cardiovasc. Res., 55, 506, 10.1016/S0008-6363(02)00414-5 FitzGerald, 2002, Cardiovascular pharmacology of nonselective nonsteroidal anti-inflammatory drugs and coxibs: clinical considerations, Am. J. Cardiol., 89, 26D, 10.1016/S0002-9149(02)02234-8 Simon, 2002, Cycle-oxygenase 2 function is essential for bone fracture healing, J. Bone Miner. Res., 17, 963, 10.1359/jbmr.2002.17.6.963 Raisz, 1999, Prostaglandins and bone: physiology and pathophysiology, Osteoarthritis Cartilage, 7, 211, 10.1053/joca.1998.0230 Harris, 1996, The macula densa: recent developments, J. Hypertens., 14, 221, 10.1097/00004872-199607000-00003 Harris Jr RC. Cyclooxygenase-2 inhibition and renal physiology. Am J Cardiol 2002;89(Suppl):10D–17D. Morham, 1995, Prostaglandin synthase 2 gene disruption causes severe renal pathology in the mouse, Cell, 83, 473, 10.1016/0092-8674(95)90125-6 Lim, 1997, Multiple female reproductive failures in cyclooxygenase 2-deficient mice, Cell, 91, 197, 10.1016/S0092-8674(00)80402-X Langenbach, 1995, Prostaglandin synthase 1 gene disruption in mice reduces arachidonic acid-induced inflammation and indomethacin-induced gastric ulceration, Cell, 83, 483, 10.1016/0092-8674(95)90126-4 Silverstein, 2000, Gastrointestinal toxicity with celecoxib versus nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: a randomized controlled trial Celecoxib Long-term Arthritis Safety Study, JAMA, 284, 1247, 10.1001/jama.284.10.1247 Bombardier, 2000, Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis, N. Engl. J. Med., 343, 1520, 10.1056/NEJM200011233432103 Food and Drug Administration. Medical Officer Review NDA 20-998/S-009 Celecoxib. 2000. Available at: http://www.fda.gov/. Food and Drug Administration, FDA Advisory Committee. Cardiovascular Safety Review of Rofecoxib. 2001. Available at: http://www.fda.gov/. Mukherjee, 2001, Risk of cardiovascular events associated with selective COX-2 inhibitors, JAMA, 286, 954, 10.1001/jama.286.8.954 Juni, 2002, Are selective COX 2 inhibitors superior to traditional nonsteroidal anti-inflammatory drugs?, BMJ, 324, 1287, 10.1136/bmj.324.7349.1287 Kargman, 1996, Characterization of prostaglandin G/H synthase 1 and 2 in rat, dog, monkey, and human gastrointestinal tracts, Gastroenterology, 111, 445, 10.1053/gast.1996.v111.pm8690211 Ristimaki, 1997, Expression of cyclooxygenase-2 in human gastric carcinoma, Cancer Res., 57, 1276 Jackson, 2000, Cyclo-oxygenase (COX) 1 and 2 in normal inflamed and ulcerated human gastric mucosa, Gut, 47, 762, 10.1136/gut.47.6.762 Gilroy, 1999, Inducible cyclooxygenase may have anti-inflammatory properties, Nat. Med., 5, 698, 10.1038/9550 Tatsuguchi, 2000, Localisation of cyclo-oxygenase 1 and cyclo-oxygenase 2 in Helicobacter pylori related gastritis and gastric ulcer tissues in humans, Gut, 46, 782, 10.1136/gut.46.6.782 Lajoie, 2002, Induction of cyclo-oxygenase-2 expression in naturally occurring gastric ulcers, J. Histochem. Cytochem., 50, 923, 10.1177/002215540205000706 Schmassmann, 1998, Effects of inhibition of prostaglandin endoperoxide synthase-2 in chronic gastro-intestinal ulcer models in rats, Br. J. Pharmacol., 123, 795, 10.1038/sj.bjp.0701672 Jones, 1999, Inhibition of angiogenesis by nonsteroidal anti-inflammatory drugs: insight into mechanisms and implications for cancer growth and ulcer healing, Nat. Med., 5, 1418, 10.1038/70995 Patrignani, 1999, COX-2 is not involved in thromboxane biosynthesis by activated human platelets, J. Physiol. Pharmacol., 50, 661 Cayatte, 2000, The thromboxane receptor antagonist S18886 but not aspirin inhibits atherogenesis in apo E-deficient mice: evidence that eicosanoids other than thromboxane contribute to atherosclerosis, Arterioscler. Thromb. Vasc. Biol., 20, 1724, 10.1161/01.ATV.20.7.1724 Pratico, 2001, Acceleration of atherogenesis by COX-1-dependent prostanoid formation in low density lipoprotein receptor knockout mice, Proc. Natl. Acad. Sci. U.S.A., 98, 3358, 10.1073/pnas.061607398 Topper, 1996, Identification of vascular endothelial genes differentially responsive to fluid mechanical stimuli: cyclooxygenase-2, manganese superoxide dismutase and endothelial cell nitric oxide synthase are selectively up-regulated by steady laminar shear stress, Proc. Natl. Acad. Sci. U.S.A., 93, 10417, 10.1073/pnas.93.19.10417 FitzGerald, 1984, Increased prostacyclin biosynthesis in patients with severe atherosclerosis and platelet activation, N. Engl. J. Med., 310, 1065, 10.1056/NEJM198404263101701 Frishman, 2002, Effect of nonsteroidal anti-inflammatory drug therapy on blood pressure and peripheral edema, Am. J. Cardiol., 89, 18D, 10.1016/S0002-9149(02)02233-6 Schlondorff, 1993, Renal complications of nonsteroidal anti-inflammatory drugs, Kidney Int., 44, 643, 10.1038/ki.1993.293 Borgeat, 1979, Transformation of arachidonic acid by rabbit polymorphonuclear leukocytes. Formation of a novel dihydroxyeicosatetraenoic acid, J. Biol. Chem., 254, 2643, 10.1016/S0021-9258(17)30120-5 Haeggström, 2001, Enzymes and receptor in the leukotriene cascade, Cell Mol. Life Sci., 59, 742, 10.1007/s00018-002-8463-1 Penrose JF, Austen KF, Lam BK. Leukotrienes: biosynthetic pathways, release and receptor-mediated actions with relevance to disease states. In: Gallin JL, Snyderman R, editors. Inflammation basic principles and clinical correlates. Philadelphia: Lippincott, Williams & Wilkins; 1999. p. 361–72. Lewis, 1990, Leukotrienes and other products of the 5-lipoxygenase pathway: biochemistry and relation to pathobiology in human diseases, N. Engl. J. Med., 323, 645, 10.1056/NEJM199009063231006 Dixon, 1988, Cloning of the cDNA for human 5-lipoxygenase, Proc. Natl. Acad. Sci. U.S.A., 85, 416, 10.1073/pnas.85.2.416 Matsumoto, 1988, Molecular cloning and amino acid sequence of human 5-lipoxygenase, Proc. Natl. Acad. Sci. U.S.A., 85, 26, 10.1073/pnas.85.1.26 Sala, 2001, Neutrophils, endothelial cells, and cysteinyl leukotrienes: a new approach to neutrophildependent inflammation?, Biochem. Biophys. Res. Commun., 283, 1003, 10.1006/bbrc.2001.4865 Borgeat, 1979, Arachidonic acid metabolism in polymorphonuclear leukocytes: effects of ionophore A23187, Proc. Natl. Acad. Sci. U.S.A., 76, 2148, 10.1073/pnas.76.5.2148 Weller, 1983, Generation and metabolism of 5-lipoxygenase pathway leukotrienes by human eosinophils: predominant production of leukotriene C4, Proc. Natl. Acad. Sci. U.S.A., 80, 7626, 10.1073/pnas.80.24.7626 MacGlashan, 1982, Generation of leukotrienes by purified human lung mast cells, J. Clin. Invest., 70, 747, 10.1172/JCI110670 Chen, 1994, Role of leukotrienes revealed by targeted disruption of the 5-lipoxygenase gene, Nature, 372, 179, 10.1038/372179a0 Goulet, 1994, Altered inflammatory responses in leukotriene-deficient mice, Proc. Natl. Acad. Sci. U.S.A., 91, 12852, 10.1073/pnas.91.26.12852 Bailie, 1996, Leukotriene-deficient mice manifest enhanced lethality from Klebsiella pneumonia in association with decreased alveolar macrophage phagocytic and bactericidal activities, J. Immunol., 157, 5221, 10.4049/jimmunol.157.12.5221 Irvin, 1997, 5-Lipoxygenase products are necessary for ovalbumin-induced airway responsiveness in mice, Am. J. Physiol., 16, L1053 Byrum, 1999, Determination of the contribution of cysteinyl leukotrienes and leukotriene B4 in acute inflammatory-responses using 5-lipoxygenase- and leukotriene A4 hydrolase-deficient mice, J. Immunol., 163, 6810, 10.4049/jimmunol.163.12.6810 Various authors. Supplement. Leukotrienes as targets for the treatment of asthma and other diseases: current basic and clinical research. Resp Clin Care Med 2000;161(2), part 2. Roberts, 1997, Leukotrienes in ulcerative colitis: results of a multicenter trial of a leukotriene biosynthesis inhibitor, MK-591, Gastroenterology, 112, 725, 10.1053/gast.1997.v112.pm9041233 Fiorucci, 2001, Dual inhibitors of cyclooxygenase and 5-lipoxygenase. A new avenue in anti-inflammatory therapy?, Biochem. Pharmacol., 62, 1433, 10.1016/S0006-2952(01)00747-X Bertolini, 2001, Dual acting anti-inflammatory drugs: a reappraisal, Pharmacol. Res., 44, 437, 10.1006/phrs.2001.0872 Bertolini, 2002, Selective COX-2 inhibitors and dual acting anti-inflammatory drugs: critical remarks, Curr. Med. Chem., 9, 1033, 10.2174/0929867024606650 Skelly, 2002, Potential alternatives to COX 2 inhibitors, BMJ, 324, 1289, 10.1136/bmj.324.7349.1289 Parente, 2001, Pros and cons of selective inhibition of cyclooxygenase-2 versus dual lipoxygenase/cyclooxygenase inhibition: is two better than one?, J. Rheumatol., 28, 2375 Cracowski, 2002, Isoprostanes as a biomarker of lipid peroxidation in humans: physiology pharmacology and clinical implications, Trends Pharmacol. Sci., 23, 360, 10.1016/S0165-6147(02)02053-9 Laufer, 1994, Pharmacological profile of a new pyrrolizine derivative inhibiting the enzymes cyclo-oxygenase and 5-lipoxygenase, Arzneimittel-Forschung, 44, 629 Laufer, 2001, Discovery and development of ML3000, Inflammopharmacology, 9, 101, 10.1163/156856001300248371 Tries, 2002, The mechanism of action of the new anti-inflammatory compound ML3000: inhibition of 5-LOX and COX-1/2, Inflamm. Res., 51, 135, 10.1007/PL00000285 Algate, 1995, General pharmacology of [2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine-5-yl]-acetic acid in experimental animals, Arzneimittel-Forschung, 45, 159 Laufer, 1995, Acute and chronic anti-inflammatory properties of [2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizne-5-yl]-acetic acid, Arzneimittel-Forschung., 45, 27 Laufer, 1994, Gastrointestinal tolerance of [2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine-5-yl]-acetic acid in the rat, Arzneimittel-Forschung., 44, 1329 Wallace, 1994, ML3000 reduces gastric prostaglandin synthesis without causing mucosal injury, Eur. J. Pharmacol., 271, 525, 10.1016/0014-2999(94)90814-1 Tries, 2001, The pharmacological profile of ML3000: a new pyrrolizine derivative inhibiting the enzymes cyclo-oxygenase and 5-lipoxygenase, Inflammopharmacology, 9, 113, 10.1163/156856001300248380 Tries, 2002, Antithrombotic and platelet function inhibiting effects of ML3000, a new anti-inflammatory drug with COX/5-LOX inhibitory activity, Inflamm. Res., 51, 129, 10.1007/PL00000284 Rotondo S, Krauze-Btzosko S, Manarini S, Martelli N, Evangelista V, Cerletti C. Licofelone (ML3000), an inhibitor of cyclooxygenase(COX)-1, COX-2 and 5-lipoxygenase (5-LOX), specifically inhibits cox-1-dependent platelet activation. Ann Rheum Dis 2002;61(Suppl 1) [abstract 46]. Atik, 1990, Leukotriene B4 and prostaglandin E2-like activity in synovial fluid in osteoarthritis, Prostaglandins Leukot. Essent. Fatty Acids, 39, 253, 10.1016/0952-3278(90)90002-3 Wittenberg, 1993, In vitro release of prostaglandins and leukotrienes from synovial tissue, cartilage, and bone in degenerative joint diseases, Arthritis Rheum., 36, 1444, 10.1002/art.1780361017 He, 2002, Synthesis of interleukin 1beta, tumor necrosis factor-alpha, and interstitial collagenase (MMP-1) is eicosanoid dependent in human osteoarthritis synovial membrane explants: interactions with anti-inflammatory cytokines, J. Rheumatol., 29, 546 Jovanovic, 2001, In vivo dual inhibition of cyclooxygenase and lipoxygenase by ML-3000 reduces the progression of experimental osteoarthritis: suppression of collagenase 1 and interleukin-1 beta synthesis, Arthritis Rheum., 44, 2320, 10.1002/1529-0131(200110)44:10<2320::AID-ART394>3.0.CO;2-P Boileau, 2002, Licofelone (ML-3000), a dual inhibitor of 5-lipoxygenase and cyclooxygenase, reduces the level of cartilage chondrocyte death in vivo in experimental dog osteoarthritis: inhibition of proapoptotic factors, J. Rheumatol., 29, 1446 Pelletier JP, Boileau C, Jouzeau JY, Netter P, Moldovan F, Laufer S, Tries S, Martel-Pelletier J. Licofelone (ML-3000), a dual inhibitor of both 5-lipoxygenase and cyclooxygenases, reduces the level of cartilage chondrocyte death in vivo in experimental dog osteoarthritis: inhibition of pro-apoptotic factors. Ann Rheum Dis 2002;61(Suppl 1) [abstract 198]. Gay, 2001, Dual inhibition of 5-lipoxygenase and cyclooxygenases 1 and 2 by ML3000 reduces joint destruction in adjuvant arthritis, J. Rheumatol., 28, 2060 Lajeunesse D, Paredes Y, Massicotte F, Martel-Pelletier J, Laufer S, Tries S. Role of leukotriene B4 in the abnormal function of human subchondral osteoarthritic osteoblasts: effects of the combined inhibition of cyclooxygenase and 5-lipoygenase (5-LO) by licofelone (ML-3000). Ann Rheum Dis 2002;61(Suppl 1) [abstract 199]. Reginster J, Bias P, Buchner A. First clinical results of licofelone (ML3000), an inhibitor of COX-1, COX-2 and 5-LOX for the treatment of osteoarthritis. Ann Rheum Dis 2002;61(Suppl 1) [abstract 189]. Klesser B, Bias P, Buchner A. Licofelone (ML3000), an inhibitor of COX-1, COX-2 and 5-LOX has little or no effect on the gastric mucosa after 4 weeks of treatment. Ann Rheum Dis 2002;61(Suppl 1) [abstract 243].