| Title | Effect of cyclooxygenase and NO synthase inhibitors on antinociceptive action of acetaminophen. | | Author(s) | Bujalska M, Gumułka WS | | Institution | Department of Pharmacodynamics, Medical University of Warsaw, Warszawa, Poland. mbujalski@profilsp.com.pl | | Source | Pol J Pharmacol 2001 Jul-Aug; 53(4):341-50. | | MeSH | Acetaminophen
Analgesics, Non-Narcotic
Animals
Cyclooxygenase 1
Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Indazoles
Isoenzymes
Lysine
Male
Membrane Proteins
Nitric Oxide Synthase
Nitric Oxide Synthase Type I
Nitric Oxide Synthase Type II
Nitroarginine
Pain Threshold
Prostaglandin-Endoperoxide Synthases
Rats
Rats, Wistar
Reaction Time
Stimulation, Chemical
Stress, Mechanical
Substrate Specificity
| | 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. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 11990080 |
|
