COX-2 in brain and spinal cord implications for therapeutic use.
Following the discovery of inducible COX-2 in arthritic joint fluid and immunocompetent cells a revolution in the field of antiinflammatory treatment was expected. The detection of a constitutive COX-2 in the kidney, in stomach and central nervous system destroyed this hypotheses. Further experiments in animal models were done to elucidate the role of the constitutive COX-2 in different physiological and pathophysiological states. In central nervous system was shown that the constitutive COX-2 is the predominant isoform of cyclooxygenases in brain and spinal cord and is highly regulated by different mediators. After experimental induction of peripheral inflammation a significant induction of COX-2 gene, protein expression and synthesis of prostaglandins in the spinal cord was detected. It was concluded that COX-2 is strongly involved in pain mediation processing in the spinal cord. The detection of COX-2 in the brain endothelial cells and its role in fever led to new insights of development and time course of temperature elevation. Probably, the use of selective COX-2 inhibitors decreases fever more effective than classical antipyretics. Furthermore, newer results show a role of COX-2 in differentiation and maturation processes in brain. These findings implicate new ways for the treatment of Alzheimer's disease and other degenerative brain disorders. Clinical and experimental results with selective COX-2 inhibitors show a better safety profile than non-selective COX inhibitors. The clinical use after drug registration will be decide on the further role of this new class of drugs in analgesic/antiinflammatory therapy and on new fields of clinical use.
Hoffmann
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Department of Experimental and Clinical Pharmacology and Toxicology, Friedrich Alexander University Erlangen-Nuremberg, Germany.
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001921:Brain / Q000201:enzymology*; D002545:Brain Ischemia / Q000188:drug therapy / Q000201:enzymology; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D005334:Fever / Q000188:drug therapy / Q000201:enzymology; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy / Q000201:enzymology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000502:physiology*; D008565:Membrane Proteins; D010146:Pain / Q000188:drug therapy / Q000201:enzymology; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D013116:Spinal Cord / Q000201:enzymology*; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000201:enzymology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases