Inhibitory effect of zacopride on Cisplatin-induced delayed emesis in ferrets

J Pharmacol Sci. 2006 May;101(1):99-102. doi: 10.1254/jphs.scj05007x. Epub 2006 Apr 29.

Abstract

We evaluated the antiemetic effect of zacopride, a potent 5-HT3-receptor antagonist with 5-HT4-receptor agonist properties, on delayed emesis caused by cisplatin (5 mg/kg, i.p.) in ferrets, compared with granisetron, a selective 5-HT3-receptor antagonist. Multiple intravenous injections of zacopride at 1 mg/kg, a dose that completely inhibited acute emesis caused bycisplatin (10 mg/kg, i.v.), significantly reduced delayed emesis. Granisetron (3.2 mg/kg) also reduced delayed emesis but this failed to reach statistical significance. The present study suggests that a combined 5-HT3-receptor antagonist/5-HT4-receptor agonist, like zacopride, may be useful against both acute and delayed emesis induced by cancer chemotherapy.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antiemetics / pharmacology*
  • Antineoplastic Agents / adverse effects*
  • Benzamides / pharmacology*
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology*
  • Cisplatin / adverse effects*
  • Drug Therapy, Combination
  • Ferrets
  • Granisetron / pharmacology
  • Male
  • Serotonin Antagonists / pharmacology*
  • Time Factors
  • Vomiting / chemically induced
  • Vomiting / prevention & control*

Substances

  • Antiemetics
  • Antineoplastic Agents
  • Benzamides
  • Bridged Bicyclo Compounds, Heterocyclic
  • Serotonin Antagonists
  • zacopride
  • Cisplatin
  • Granisetron