ANTINEOPLASTIC ACTIVITY AND TOLERABILITY OF A NOVEL HETEROCYCLIC ALKYLPHOSPHOLIPID, D-20133

Octadecyl-[2-(N-methylpiperidinio)ethyl]-phosphate (OMPEP, D-20133), a heterocyclic analogue of hexadecylphosphocholine (MIL), has been synt hesized in an attempt to increase the therapeutic range of the parent compound. The antineoplastic activity of the novel alkylphospholipid w as compared with that of MIL in dimethyl-benz(a)anthracene-induced mam mary carcinoma of the rat. Using tumors of different sizes and repeate d daily doses as well as high single doses, we achieved marked remissi ons with either compound. However, the therapeutic range of OMPEP was broader than that of the parent drug. Furthermore, the emetic potentia l of OMPEP tested on ferrets was distinctly less pronounced than that of MIL. In vitro the new alkylphospholipid proved to be more active th an MIL in all cell lines tested, and its differentiation-inducing capa city turned out to be superior to that of MIL. No hematological toxici ty was observed at various OMPEP doses during a 3-week treatment perio d.