Non-steroidal anti-inflammatory drugs react with two sites on platelet cyclo-oxygenase evidence from 'in vivo' drug interaction studies in rats

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Abstract

Non-steroidal anti-inflammatory drugs inhibit platelet cylco-oxygenase activity. This study shows that salicylate, diflunisal, sulphinpyrazone and indomethacine prevent in vivo aspirin inhibitory effect of cyclo-oxygenase activity as measured by the formation of malondialdehyde and thromboxane B2, two products of platelet arachidonic acid metabolism. Salicylate also prevents the inhibitory effect of indomethacin. All these drugs therefore appear to interact with the same site on platelet cyclo-oxygenase. Since salicylate is inactive by itself on this platelet enzyme and diflunisal and sulphinpyrazone were used at ineffective doses, it is suggested that their interaction with aspirin (or indomethacin) occurs at the level of a supplementary site is necessary but not sufficient for the efficacy of these drugs as cyclo-oxygenase inhibitors. Acetylation by aspirin of the active site appears to be a phenomenon secondary to the binding of salicylate moiety to the supplementary site.

Original languageEnglish
Pages (from-to)122-128
Number of pages7
JournalBBA - General Subjects
Volume714
Issue number1
DOIs
Publication statusPublished - Jan 12 1982

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Drug interactions
Salicylates
Prostaglandin-Endoperoxide Synthases
Platelets
Drug Interactions
Rats
Anti-Inflammatory Agents
Blood Platelets
Diflunisal
Sulfinpyrazone
Aspirin
Indomethacin
Pharmaceutical Preparations
Acetylation
Oxygenases
Thromboxane B2
Cyclooxygenase Inhibitors
Malondialdehyde
Arachidonic Acid
Metabolism

Keywords

  • (Rat platelet)
  • Anti-inflammatory drug
  • Cyclo-oxygenase
  • Drug interaction

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology
  • Medicine(all)

Cite this

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title = "Non-steroidal anti-inflammatory drugs react with two sites on platelet cyclo-oxygenase evidence from 'in vivo' drug interaction studies in rats",
abstract = "Non-steroidal anti-inflammatory drugs inhibit platelet cylco-oxygenase activity. This study shows that salicylate, diflunisal, sulphinpyrazone and indomethacine prevent in vivo aspirin inhibitory effect of cyclo-oxygenase activity as measured by the formation of malondialdehyde and thromboxane B2, two products of platelet arachidonic acid metabolism. Salicylate also prevents the inhibitory effect of indomethacin. All these drugs therefore appear to interact with the same site on platelet cyclo-oxygenase. Since salicylate is inactive by itself on this platelet enzyme and diflunisal and sulphinpyrazone were used at ineffective doses, it is suggested that their interaction with aspirin (or indomethacin) occurs at the level of a supplementary site is necessary but not sufficient for the efficacy of these drugs as cyclo-oxygenase inhibitors. Acetylation by aspirin of the active site appears to be a phenomenon secondary to the binding of salicylate moiety to the supplementary site.",
keywords = "(Rat platelet), Anti-inflammatory drug, Cyclo-oxygenase, Drug interaction",
author = "Chiara Cerletti and Manuela Livio and {De Gaetano}, Giovanni",
year = "1982",
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AU - Cerletti, Chiara

AU - Livio, Manuela

AU - De Gaetano, Giovanni

PY - 1982/1/12

Y1 - 1982/1/12

N2 - Non-steroidal anti-inflammatory drugs inhibit platelet cylco-oxygenase activity. This study shows that salicylate, diflunisal, sulphinpyrazone and indomethacine prevent in vivo aspirin inhibitory effect of cyclo-oxygenase activity as measured by the formation of malondialdehyde and thromboxane B2, two products of platelet arachidonic acid metabolism. Salicylate also prevents the inhibitory effect of indomethacin. All these drugs therefore appear to interact with the same site on platelet cyclo-oxygenase. Since salicylate is inactive by itself on this platelet enzyme and diflunisal and sulphinpyrazone were used at ineffective doses, it is suggested that their interaction with aspirin (or indomethacin) occurs at the level of a supplementary site is necessary but not sufficient for the efficacy of these drugs as cyclo-oxygenase inhibitors. Acetylation by aspirin of the active site appears to be a phenomenon secondary to the binding of salicylate moiety to the supplementary site.

AB - Non-steroidal anti-inflammatory drugs inhibit platelet cylco-oxygenase activity. This study shows that salicylate, diflunisal, sulphinpyrazone and indomethacine prevent in vivo aspirin inhibitory effect of cyclo-oxygenase activity as measured by the formation of malondialdehyde and thromboxane B2, two products of platelet arachidonic acid metabolism. Salicylate also prevents the inhibitory effect of indomethacin. All these drugs therefore appear to interact with the same site on platelet cyclo-oxygenase. Since salicylate is inactive by itself on this platelet enzyme and diflunisal and sulphinpyrazone were used at ineffective doses, it is suggested that their interaction with aspirin (or indomethacin) occurs at the level of a supplementary site is necessary but not sufficient for the efficacy of these drugs as cyclo-oxygenase inhibitors. Acetylation by aspirin of the active site appears to be a phenomenon secondary to the binding of salicylate moiety to the supplementary site.

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KW - Anti-inflammatory drug

KW - Cyclo-oxygenase

KW - Drug interaction

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