The effects of orally administered Y-25130, a selective serotonin3-receptor antagonist, on chemotherapeutic agent-induced emesis.

The antiemetic effects of orally administered Y-25130, a potent and selective 5-HT3-receptor antagonist, were compared with those of ondansetron, granisetron, metoclopramide and domperidone. Y-25130 (0.1-1.0 mg/kg) dose-dependently prolonged the latency to the first vomiting and decreased the number of vomitings induced by cisplatin in dogs. The antiemetic effect of Y-25130 against cisplatin-induced vomiting was more potent than that of metoclopramide and ondansetron, but it showed little difference from that of granisetron. The emesis induced by the combined treatment of doxorubicin and cyclophosphamide was also inhibited by Y-25130 (0.1-1 mg/kg) in ferrets. The antiemetic effect of Y-25130 was more potent than that of metoclopramide, almost the same as that of granisetron and less potent than that of ondansetron. Because of a notable difference of potency ranking between Y-25130 and ondansetron in these two tests, a third test was performed to evaluate the inhibitory effect of Y-25130 in ferrets on cisplatin-induced emesis in comparison with that of ondansetron. The antiemetic effect of Y-25130 on cisplatin-induced emesis in ferrets was very similar to that of ondansetron. Domperidone did not inhibit these cytotoxic agents-induced emeses. These results suggest that Y-25130 is an orally active antiemetic compound against cisplatin and doxorubicin/cyclophosphamide-induced emeses; and its the antiemetic potency is similar to those of granisetron and ondansetron, but superior to those of metoclopramide and domperidone.