Nakayama Hiroe, Yamakuni Hisashi, Nakayama Aya, Maeda Yasue, Imazumi Katsunori, Matsuo Masahiko, Mutoh Seitaro
Department of Urology, Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
J Pharmacol Sci. 2004 Nov;96(3):301-6. doi: 10.1254/jphs.fpj04035x. Epub 2004 Nov 5.
Previous studies showed that diphenidol was effective on emetogens-induced pica, eating of non-nutritive substances, in rats, a model analogous to emesis in other species. We evaluated the actual antiemetic activity of diphenidol against four emetic stimuli in the dog and ferret, animals that possess an emetic reflex. In dogs, emetic responses to apomorphine were significantly prevented by diphenidol (3.2 mg/kg, i.v.), whereas diphenidol (3.2 mg/kg, i.v. x 2) showed a weak inhibition to the vomiting evoked by cisplatin. In ferrets, diphenidol (10 mg/kg, i.p.) exhibited a weak antiemetic activity on the emesis induced by copper sulfate and had no activity on emesis by loperamide. On the other hand, CP-122,721, a NK1-receptor antagonist, significantly reduced the emetic episodes to all four stimuli. These results suggest that the prediction of antiemetic activity of compounds in animals lacking an emetic reflex does not always correspond with actual antiemetic activity.
先前的研究表明，在大鼠中，地芬尼多对催吐剂诱导的异食癖（即食用非营养物质）有效，大鼠是一种类似于其他物种呕吐的模型。我们评估了地芬尼多对具有呕吐反射的犬和雪貂的四种催吐刺激的实际止吐活性。在犬中，地芬尼多（3.2mg/kg，静脉注射）可显著预防对阿扑吗啡的呕吐反应，而地芬尼多（3.2mg/kg，静脉注射×2）对顺铂诱发的呕吐显示出微弱的抑制作用。在雪貂中，地芬尼多（10mg/kg，腹腔注射）对硫酸铜诱导的呕吐表现出微弱的止吐活性，而对洛哌丁胺引起的呕吐无活性。另一方面，NK1受体拮抗剂CP-122,721显著减少了对所有四种刺激的呕吐发作。这些结果表明，在缺乏呕吐反射的动物中预测化合物的止吐活性并不总是与实际止吐活性相符。
