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
Year2007
Month2
Day1
Volume Number103
Issue Number2
PublisherJAPANESE PHARMACOLOGICAL SOC
Pages189 - 200
ISSN1347-8613
eISSN1347-8648
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