Action of 5-HT3 receptor antagonists and dexamethasone to modify cisplatin-induced emesis in Suncus murinus (house musk shrew).
Ondansetron (1-3 mg/kg), granisetron (0.3-1 mg/kg) and dexamethasone (0.3-1 mg/kg), administered at 12-h intervals, were investigated for their potential to prevent cisplatin (30 mg/kg, i.p.)-induced emesis during a 72-h observation period. Ondansetron appeared more active than granisetron to antagonise the emetic response occurring in the first 4-h (P<0.05) period, but none of the regimens significantly antagonised emesis during the 0-24- and 24-72-h periods (P>0.05). However, ondansetron was more active to antagonise emesis on day 1 using a more frequent drug administration, whereas bilateral vagotomy only reduced emesis for 2 h, and 5-HT, 2-methyl-5-HT and 1-m-chloro-phenylbiguanide (up to 20-30 mg/kg, i.p.) were not emetic. The combination of ondansetron 1 mg/kg and dexamethasone 1 mg/kg, both administered every 12 h, significantly delayed the onset of emesis (P<0.05) but failed to reduce the total numbers of retches+vomits over the 3-day period (P>0.05). Results are discussed in relation to the clinical situation.
Sam
Tasia S W
TS
Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, SAR, China.
Cheng
Jimmy T Y
JT
Johnston
Kevin D
KD
Kan
Kelvin K W
KK
Ngan
Man P
MP
Rudd
John A
JA
Wai
Man K
MK
Yeung
John H K
JH
D000818:Animals; D000932:Antiemetics / Q000008:administration & dosage / Q000627:therapeutic use*; D002945:Cisplatin / Q000633:toxicity*; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004947:Esophagus / Q000294:innervation; D005260:Female; D017829:Granisetron / Q000008:administration & dosage / Q000627:therapeutic use; D007274:Injections, Intraperitoneal; D008297:Male; D017294:Ondansetron / Q000008:administration & dosage / Q000627:therapeutic use; D058831:Serotonin 5-HT3 Receptor Antagonists; D012788:Shrews; D014628:Vagotomy; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*
D000932:Antiemetics; D002945:Cisplatin; D003907:Dexamethasone; D017829:Granisetron; D017294:Ondansetron; D058831:Serotonin 5-HT3 Receptor Antagonists