Effect of several d-morphinans on ascites tumors in mice

Dextromethorphan and its analogues (DM 16, DM 34, DM 72, DM 75 and DM 96) were examined for their effect on Ehrlich ascites carcinoma or ascites sarcoma-180 in female mice of the ddY strain. The suspension of Ehrlich carcinoma cells or sarcoma-180 cells was prepared from mice at 10 days after i.p. inoculation of the cells, using Hanks' balanced salt solution, and the cell suspension was inoculated i.p. into mice (2 X 10(6) viable cells/mouse). The chemicals dissolved in physiological saline containing 5% HCO-60 were then injected i.p. into the mice once daily for 5 successive days (5-40 mg/kg/day). In addition, mice given the tumor cells were treated with the saline containing 5% HCO-60 alone for 5 days (untreated mice). In groups of mice bearing Ehrlich ascites carcinoma or ascites sarcoma-180, the mean survival time of mice treated with 20-40 mg/kg/day of DM 96 was more than twice that of the corresponding untreated mice. The mean survival time of mice treated with 20 mg/kg/day of DM 96 was also longer than that of mice treated with 40 mg/kg/day of the other chemicals, irrespective of the ascites tumors. Concerning these survival times, the LD50 (i.p.) of DM 96 in mice differed slightly from that of other chemicals (88 mg/kg and 77-106 mg/kg). These results indicate that DM 96 is more active than the other chemicals against the ascites tumors in mice.