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Titolo:
Measurement of differential inhibition of COX-1 and COX-2 and the pharmacology of selective inhibitors
Autore:
Pairet, M; van Ryn, J;
Indirizzi:
Boehringer Ingelheim KG, Resp Res, D-88397 Biberach, Germany Boehringer Ingelheim KG Biberach Germany D-88397 88397 Biberach, Germany
Titolo Testata:
DRUGS OF TODAY
fascicolo: 4-5, volume: 35, anno: 1999,
pagine: 251 - 265
SICI:
0025-7656(199904/05)35:4-5<251:MODIOC>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
NONSTEROIDAL ANTIINFLAMMATORY DRUGS; PROSTAGLANDIN-G/H SYNTHASE-1; ANTI-INFLAMMATORY DRUGS; PLATELET-AGGREGATION; WHOLE-BLOOD; CYCLOOXYGENASE-2 INHIBITOR; COX-2-SELECTIVE INHIBITOR; ENDOPEROXIDE SYNTHASES; RHEUMATOID-ARTHRITIS; PLASMA-CONCENTRATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
87
Recensione:
Indirizzi per estratti:
Indirizzo: Pairet, M Boehringer Ingelheim KG, Resp Res, Birkendorfer Str 65, D-88397 Biberach, Germany Boehringer Ingelheim KG Birkendorfer Str 65 Biberach Germany D-88397
Citazione:
M. Pairet e J. van Ryn, "Measurement of differential inhibition of COX-1 and COX-2 and the pharmacology of selective inhibitors", DRUGS TODAY, 35(4-5), 1999, pp. 251-265

Abstract

Since the discovery of a second isoenzyme of cyclooxygenase (COX)-2, it has been hypothesized that the antiinflammatory effects of nonsteroidal antiinflammatory drugs (NSAIDs) are dependent on their inhibition of COX-2, whereas inhibition of constitutive COX-1 is responsible for their gastric and renal side effects as well as for inhibition of platelet activation. Consequently, a large number of in vitro assays have been developed to characterize the COX-1 and COX-2 inhibitory activities of NSAIDs in order to look for compounds with preferential inhibition of COX-2. Depending on the test system, however, the experimental conditions may vary greatly, thereby affecting the outcome. These important variables include the source of enzymes COX-1 and COX-2 (human or animal); the cell system used (intact normal cells ortransfected cell lines); the method of enzyme preparation (purified enzymes, microsomal or whole cell assays); the COX-2-inducing agent; the source of arachidonic acid and its concentration; the incubation time with drug, inducing agent or arachidonic acid; and the protein concentration in the medium. Depending on the test system employed for defining the IC50 for COX-1 and COX-2 inhibition, the resultant ratio between these activities may lead to divergent and confusing comparisons. We review the various in vitro testsystems available for the measurement of COX-1 and COX-2 inhibition. The use of human recombinant enzymes and the human whole blood assay are examined in detail. The relevance of these test systems to in vivo animal models of inflammation and the side effects of NSAIDs (e.g., gastric mucosal and renal damage) is assessed. Finally, the results of clinical studies on the effect of inhibiting COX-1 and COX-2 activity is summarized. (C) 1999 Prous Science. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 07/07/20 alle ore 18:38:25