title: Antineoplastic activity and tolerability of a novel heterocyclic alkylphospholipid, D-20133.
abstract: Octadecyl-[2-(N-methylpiperidinio)ethyl]-phosphate (OMPEP, D-20133), a heterocyclic analogue of hexadecylphosphocholine (MIL), has been synthesized in an attempt to increase the therapeutic range of the parent compound. The antineoplastic activity of the novel alkylphospholipid was compared with that of MIL in dimethylbenz(a)anthracene-induced mammary carcinoma of the rat. Using tumors of different sizes and repeated daily doses as well as high single doses, we achieved marked remissions with either compound. However, the therapeutic range of OMPEP was broader than that of the parent drug. Furthermore, the emetic potential of OMPEP tested on ferrets was distinctly less pronounced than that of MIL. In vitro the new alkylphospholipid proved to be more active than MIL in all cell lines tested, and its differentiation-inducing capacity turned out to be superior to that of MIL. No hematological toxicity was observed at various OMPEP doses during a 3-week treatment period.
authors.affiliation: Department of Experimental Cancer Research, ASTA Medica AG, Frankfurt/Main, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Stekar
authors.forename: P
authors.initials: P
authors.lastname: Hilgard
authors.forename: R
authors.initials: R
authors.lastname: Voegeli
authors.forename: H R
authors.initials: HR
authors.lastname: Maurer
authors.forename: J
authors.initials: J
authors.lastname: Engel
authors.forename: B
authors.initials: B
authors.lastname: Kutscher
authors.forename: G
authors.initials: G
authors.lastname: Nössner
authors.forename: W
authors.initials: W
authors.lastname: Schumacher
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000633:toxicity; D002454:Cell Differentiation / Q000187:drug effects; D005260:Female; D005289:Ferrets; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D010880:Piperidines / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D014407:Tumor Cells, Cultured; D014839:Vomiting / Q000139:chemically induced
chemical_list: D000970:Antineoplastic Agents; D010880:Piperidines; D010767:Phosphorylcholine; C084837:octadecyl-(2-(N-methylpiperidino)ethyl)phosphate; C039128:miltefosine; D015127:9,10-Dimethyl-1,2-benzanthracene