title: Effect of cyclooxygenase and NO synthase inhibitors on antinociceptive action of acetaminophen.
abstract: The influence of cyclooxygenase (COX) and NO synthase inhibitors on antinociceptive action of acetaminophen (ACETA) was studied in rats. ACETA increased the nociceptive threshold for both mechanical (Randall-Selitto test) and chemical stimuli (writhing test). In both models the existence of ceiling dose of ACETA was observed. Indomethacin (IND), an inhibitor preferentially acting on COX-1, as well as nimesulide (NIM) and celecoxib (CECOX), i.e. respectively preferential and selective inhibitors of COX-2, markedly decreased the antinociceptive activity of ACETA in Randall-Selitto test. In contrast, IND increased, whereas both NIM and CECOX did not have any effect on ACETA action in writhing test. Pretreatment with LG-nitro-L-arginine (L-NO-ARG), an unspecific inhibitor of NO synthase, 7-nitroindazole (7-NI), relatively specific inhibitor of neuronal NO synthase, and L-N6(1-iminoethyl)lysine (L-NIL), relatively selective inhibitor of inducible NO synthase, significantly increased the action of the lower doses of ACETA (50 and 100 mg/kg) in writhing test, whereas it did not modify the effects of the higher doses. Similar effect of L-NO-ARG and 7-NI was observed in Randall-Selitto test, whereas L-NIL did not influence the action of ACETA. The possible involvement of COX and NO synthase systems in antinociceptive activity of ACETA is discussed.
authors: Department of Pharmacodynamics, Medical University of Warsaw, Warszawa, Poland. mbujalski@profilsp.com.pl
authors: M
authors: M
authors: Bujalska
authors: W S
authors: WS
authors: Gumułka
mesh_terms: D000082:Acetaminophen / Q000494:pharmacology* / Q000627:therapeutic use; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007191:Indazoles / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008239:Lysine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D019335:Nitroarginine / Q000494:pharmacology; D017288:Pain Threshold / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D013268:Stimulation, Chemical; D013314:Stress, Mechanical; D013379:Substrate Specificity
chemical_list: D018712:Analgesics, Non-Narcotic; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D007191:Indazoles; D007527:Isoenzymes; D008565:Membrane Proteins; C090663:N(6)-(1-iminoethyl)lysine; D019335:Nitroarginine; D000082:Acetaminophen; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; C496322:Nos1 protein, rat; C496318:Nos2 protein, rat; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; D008239:Lysine; C080122:7-nitroindazole