Meloxicam: influence on arachidonic acid metabolism. Part 1. In vitro findings.
Meloxicam is a new nonsteroidal anti-inflammatory drug (NSAID) derived from enolic acid. Meloxicam has shown potent anti-inflammatory activity in animal models together with low gastrointestinal and renal toxicity. Studies were undertaken to compare meloxicam to other NSAIDS in their ability to inhibit either constitutive cyclooxygenase (COX-1) or inducible cyclooxygenase (COX-2). COX-1 was isolated as a cell-free enzyme from bovine seminal vesicles or bovine brain or was present in nonstimulated macrophages derived from the guinea-pig peritoneum. COX-2 was induced in peritoneal macrophages stimulated by lipopolysaccharide (LPS) or isolated as a cell-free enzyme from sheep placenta. Of all NSAIDs tested, meloxicam was the most selective inhibitor of COX-2 in intact cells. In cell-free enzyme preparations, however, meloxicam showed the same activity against COX-1 and COX-2. All other NSAIDs tested were more potent inhibitors of COX-1 than of COX-2. The inducible cyclooxygenase COX-2 has been implicated in the mediation of the inflammatory reaction, whereas the products of the constitutive cyclooxygenase COX-1 have cytoprotective effects in the gastric mucosa, support microcirculation in the kidney, and are antithrombogenic. Therefore, differential inhibitory effects of NSAIDs on COX-1 and COX-2 may have a bearing on the risk-benefit profile displayed in clinical practice. Meloxicam shows a preferential inhibitory effect on COX-2 over COX-1, which may be directly related to the favorable tolerability profile with potent anti-inflammatory effects observed in animal studies.
Engelhardt
G
G
Department of Pharmacological Research, Dr. Karl Thomae GmbH, Biberach/Riss, Germany.
Bögel
R
R
Schnitzer
C
C
Utzmann
R
R
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000378:metabolism*; D001921:Brain / Q000201:enzymology; D002417:Cattle; D002474:Cell-Free System; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis; D006168:Guinea Pigs; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000378:metabolism; D008297:Male; D000077239:Meloxicam; D010920:Placenta / Q000201:enzymology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D012669:Seminal Vesicles / Q000201:enzymology; D012756:Sheep; D013843:Thiazines / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008070:Lipopolysaccharides; D013843:Thiazines; D013844:Thiazoles; D016718:Arachidonic Acid; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D000077239:Meloxicam