Action of 5-HT3 receptor antagonists and dexamethasone to modify cisplatin-induced emesis in Suncus murinus (house musk shrew)

Eur J Pharmacol. 2003 Jul 4;472(1-2):135-45. doi: 10.1016/s0014-2999(03)01863-6.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiemetics / administration & dosage
  • Antiemetics / therapeutic use*
  • Cisplatin / toxicity*
  • Dexamethasone / administration & dosage
  • Dexamethasone / therapeutic use*
  • Drug Therapy, Combination
  • Esophagus / innervation
  • Female
  • Granisetron / administration & dosage
  • Granisetron / therapeutic use
  • Injections, Intraperitoneal
  • Male
  • Ondansetron / administration & dosage
  • Ondansetron / therapeutic use
  • Serotonin 5-HT3 Receptor Antagonists*
  • Shrews*
  • Vagotomy
  • Vomiting / chemically induced
  • Vomiting / prevention & control*

Substances

  • Antiemetics
  • Serotonin 5-HT3 Receptor Antagonists
  • Ondansetron
  • Dexamethasone
  • Cisplatin
  • Granisetron