Inhibitory Effect of Zacopride on Cisplatin-Induced Delayed Emesis in Ferrets

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  • Yamakuni Hisashi
    Department of Urology, Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Japan
  • Nakayama Hiroe
    Department of Urology, Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Japan
  • Matsui Shigeo
    Department of Urology, Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Japan
  • Imazumi Katsunori
    Department of Urology, Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Japan
  • Matsuo Masahiko
    Department of Urology, Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Japan
  • Mutoh Seitaro
    Department of Urology, Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Japan

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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 by cisplatin (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.<br>

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