Action of cyclooxygenase inhibitors and a leukotriene biosynthesis inhibitor on cisplatin-induced acute and delayed emesis in the ferret.
Cisplatin 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 48 h]. 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 L-745,337 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, i.p., three times per day) did not antagonize cisplatin-induced acute delayed retching + vomiting and had a different profile compared to the action of dexamethasone (1 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.
Sam
Tasia S W
TS
Emesis Research Group, Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China.
Ngan
Man P
MP
Riendeau
Denis
D
Robichaud
Annette
A
Rudd
John A
JA
D000818:Animals; D000970:Antineoplastic Agents; D002945:Cisplatin; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D004338:Drug Combinations; D005289:Ferrets / Q000502:physiology*; D005334:Fever / Q000139:chemically induced / Q000517:prevention & control; D006930:Hyperalgesia / Q000139:chemically induced / Q000517:prevention & control; D007189:Indans / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D020024:Leukotriene Antagonists / Q000494:pharmacology*; D015289:Leukotrienes / Q000096:biosynthesis; D008297:Male; D009919:Orchiectomy; D011453:Prostaglandins / Q000096:biosynthesis; D014839:Vomiting / Q000139:chemically induced* / Q000517:prevention & control*
D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D004338:Drug Combinations; D007189:Indans; C093700:L 745337; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D011453:Prostaglandins; D003907:Dexamethasone; D002945:Cisplatin; D007213:Indomethacin