Influence of iproniazid on the combination effect of reserpine with antitumor agents on l1210

The influence of two antidepressants, iproniazid and imipramine, was examined on the antileukemic combination effect of reserpine with 1-gamma-chloropropyl-2-chloromethylpiperidine hydrobromide (CAP-2), mitomycin C, or vinblastine on L1210. While reserpine synergistically increased the life span at the dose of 2.5 mg/kg in combination with these antitumor agents, the mice given reserpine showed considerable reduction of food intake and hypothermia. Iproniazid reduced all these effects of reserpine, while imipramine slightly potentiated hypothermia among these effects of reserpine. Starvation scarcely influenced the effect of the antitumor agents. On the other hand, reserpine also enhanced the antiproliferating effect of CAP-2 against L1210 cells in vitro. Iproniazid did not influence the combined antiproliferating effect of these agents in vitro. These results indicate that iproniazid reduced the antileukemic combination effect of reserpine with antitumor agents through an antireserpic effect such as inhibition of hypothermia. Therefore, it seems likely that the antileukemic combination effect of reserpine is closely related to the marked hypothermia, and only partially related to the direct effect on L1210 cells.