Cyclic amines are selective cytotoxic agents for pigmented cells.

We have shown that morpholine, a cyclic amine, exerts a selective inhibition of growth on melanocytic pigmented cell lines compared to nonpigmented cells. The ID50 of morpholine for the pigmented B-16 cell line HFH was 1200 micrograms/ml, compared to values greater than 2400 micrograms/ml for baby hamster kidney, Chinese hamster ovary and NP, an unpigmented primate cell line. Two other cyclic amines piperazine and piperidine, were similarly found to be selectively toxic to melanocytes. This selective toxicity could be synergistically enhanced by pretreatment of the cells with theophylline, a stimulator of tyrosinase activity, which indicates that the selective toxicity may be associated with melanin synthesis. Low passage HFH, high passage HFH and Syrian hamster melanoma RPMI 1846 cells that were pretreated with theophylline showed between 13 and 29% greater toxicity compared to controls treated with theophylline or morpholine alone. Unpigmented NP primate cells, Chinese hamster ovary and mouse fibroblast L929 remained unaffected. These cyclic amines join a list of other amines that have also been shown to be melanocytotoxic.