Sagrada A, Turconi M, Bonali P, Schiantarelli P, Micheletti R, Montagna E, Nicola M, Algate D R, Rimoldi E M, Donetti A
Instituto De Angeli (Boehringer Ingelheim Italia), Milano.
Cancer Chemother Pharmacol. 1991;28(6):470-4. doi: 10.1007/BF00685825.
The antiemetic activity of DAU 6215, a novel antagonist of 5-HT3 receptors, was investigated in animal models of cytotoxic treatment-evoked emesis and compared with the antiemetic activity of ondansetron and metoclopramide. In dogs, vomiting was induced by i.v. cisplatin; in ferrets, the emetic response was elicited by i.v. doxorubicin or X-ray exposure. Pretreatment with 0.1-1 mg/kg DAU 6215 given i.v. or p.o. prevented the vomiting response to the different emetic agents. In the dog, the antiemetic potency of metoclopramide was 30 times lower than that of DAU 6215. Ondansetron was less potent than DAU 6215 against cisplatin and doxorubicin but was equally effective in the radiotherapy protocol. In this model, lengthening of the pretreatment time to 2 h did not affect the antiemetic efficacy of DAU 6215, whereas it decreased that of ondansetron. The results demonstrate that DAU 6215 is a highly effective and long-lasting inhibitor of cytotoxic treatment-induced emesis in different animal species.
新型5-HT3受体拮抗剂DAU 6215的止吐活性在细胞毒性治疗诱发呕吐的动物模型中进行了研究，并与昂丹司琼和甲氧氯普胺的止吐活性进行了比较。在犬中，静脉注射顺铂诱导呕吐；在雪貂中，静脉注射阿霉素或X射线照射引发呕吐反应。静脉注射或口服给予0.1-1mg/kg DAU 6215预处理可预防对不同催吐剂的呕吐反应。在犬中，甲氧氯普胺的止吐效力比DAU 6215低30倍。昂丹司琼对顺铂和阿霉素的效力低于DAU 6215，但在放射治疗方案中效果相同。在该模型中，将预处理时间延长至2小时不影响DAU 6215的止吐疗效，而会降低昂丹司琼的止吐疗效。结果表明，DAU 6215是不同动物物种中细胞毒性治疗诱导呕吐的高效和长效抑制剂。
