Action of cyclooxygenase inhibitors and a leukotriene biosynthesis inhibitor on cisplatin-induced acute and delayed emesis in the ferret
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AbstractCisplatin at 5 mg/kg, i.p. induced an acute (day 1) and delayed (days 2 and 3) emetic response in the ferret that was used to investigate the anti-emetic activity of the non-selective cyclooxygenase inhibitor indomethacin (3 - 30 mg/kg, i.p., three times per day) and two cyclooxygenase-2 inhibitors, DFU [5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl)phenyl-2(5H)-furanone; 1 - 10 mg/kg, i.p. administered at 40 and 48 h] and L-745,337 [5-methanesulphonamido-6-(2,4-diflurothiophenyl)-1-indanone; 10 mg/kg,i.p., administered at 40 and 48h]. Only indomethacin potentiated significantly cisplatin-induced retching + vomiting (P < 0.05); DFU antagonized delayed emesis (P < 0.05) but the action was not dose-related and L745,337 was inactive (P > 0.05). However, indomethacin alone (30 mg/kg) also induced emesis (P < 0.05). The leukotriene biosynthesis inhibitor, MK-886 {3-[1-(p-chlorobenzyl)-5-(isopropyl)3-tert-butylthioindol-2-yl]-2,2-dimethylpropanoic acid; 1 - 10 mg/kg, i.p., three times per day} had no action to modify cisplatin-induced emesis (P > 0.05). The combination treatment of indomethacin (10 mg/kg, i.p., three times per day) with MK-886 (10 mg/kg, Lp., three times per day) did not antagonize cisplatin-induced acute delayed retching + vomiting and had a different profile compared to the action of dexamethasone (I mg/kg, i.p., three times per day; P < 0.05). Inhibition of the cyclooxygenase and lipoxygenase pathways does not account for the anti-emetic of dexamethasone.
All Author(s) ListSam TSW, Ngan MP, Riendeau D, Robichaud A, Rudd JA
Journal nameJournal of Pharmacological Sciences
Volume Number103
Issue Number2
Pages189 - 200
LanguagesEnglish-United Kingdom
Keywordscisplatin; cyclooxygenase; dexamethasone; emesis; leukotriene
Web of Science Subject CategoriesPharmacology & Pharmacy; PHARMACOLOGY & PHARMACY

Last updated on 2020-27-05 at 03:18