Action of metyrapone and tetracosactrin to modify cisplatin-induced acute and delayed emesis in the ferret.
Cisplatin 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 potential anti-emetic activity of metyrapone and tetracosactrin and their potential interaction. The 11beta-hydroxylase enzymes inhibitor metyrapone 10-30 mg/kg, i.p., dose dependently potentiated the acute cisplatin-induce retching+vomiting response by up to 219% at the highest dose (P<0.001) but failed to affect significantly delayed emesis (P>0.05). The adrenocorticotropic hormone (ACTH) mimetic tetracosactrin 0.1 mg/kg, i.m., antagonised significantly the acute and delayed emetic response by 98% (P<0.01) and 75% (P<0.001), respectively. The anti-emetic action of tetracosactrin on acute but not delayed emesis was prevented by combination with metyrapone 10 mg/kg, i.p. Tetracosactrin 0.1 mg/kg, i.m., failed to modify apomorphine (0.25 mg/kg, s.c.)-induced emesis. The potential anti-emetic mechanism of action of metyrapone and tetracosactrin to modulate emesis is discussed.
Sam
Tasia S W
TS
Emesis Research Group, Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., SAR, Hong Kong, China.
Kan
Kelvin K W
KK
Ngan
Man P
MP
Rudd
John A
JA
Yeung
John H K
JH
D000208:Acute Disease; D000818:Animals; D000932:Antiemetics / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001058:Apomorphine / Q000008:administration & dosage / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects*; D003366:Cosyntropin / Q000494:pharmacology / Q000627:therapeutic use*; D005289:Ferrets; D007273:Injections, Intramuscular; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008297:Male; D008797:Metyrapone / Q000494:pharmacology / Q000627:therapeutic use*; D013252:Steroid 11-beta-Hydroxylase / Q000037:antagonists & inhibitors / Q000378:metabolism; D013997:Time Factors; D014839:Vomiting / Q000139:chemically induced*
D000932:Antiemetics; D000970:Antineoplastic Agents; D003366:Cosyntropin; D013252:Steroid 11-beta-Hydroxylase; D001058:Apomorphine; D002945:Cisplatin; D008797:Metyrapone