Yamakuni Hisashi, Nakayama Hiroe, Matsui Shigeo, Imazumi Katsunori, Matsuo Masahiko, Mutoh Seitaro
Department of Urology, Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Yodogawa, Osaka, Japan.
J Pharmacol Sci. 2006 May;101(1):99-102. doi: 10.1254/jphs.scj05007x. Epub 2006 Apr 29.
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.
我们评估了扎考必利（一种具有5-HT4受体激动剂特性的强效5-HT3受体拮抗剂）对雪貂顺铂（5mg/kg，腹腔注射）引起的迟发性呕吐的止吐作用，并与选择性5-HT3受体拮抗剂格拉司琼进行了比较。多次静脉注射1mg/kg的扎考必利（该剂量可完全抑制顺铂（10mg/kg，静脉注射）引起的急性呕吐）可显著减少迟发性呕吐。格拉司琼（3.2mg/kg）也可减少迟发性呕吐，但未达到统计学意义。本研究表明，像扎考必利这样的5-HT3受体拮抗剂/5-HT4受体激动剂组合可能对癌症化疗引起的急性和迟发性呕吐均有效。
