Convulsive syndrome induced by the intracerebroventricular injection of alpha-difluoromethylornithine in rats.
In adult rats, the intracerebroventricular injection of alpha-difluoromethylornithine (DFMO), a polyamine antimetabolite which specifically inhibits ornithine-decarboxylase, induces a typical convulsive syndrome (ED50 = 100 micrograms/rat) and death (LD50 = 300 micrograms/rat). Histological lesions are seen only with the highest doses and are essentially restricted to the Ammon's horn neurones. Since DFMO is currently undergoing clinical trials for use in cancer chemotherapy, including brain tumours, its CNS toxicity should be carefully considered.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D000518:Eflornithine; D005260:Female; D007276:Injections, Intraventricular; D009952:Ornithine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D065108:Ornithine Decarboxylase Inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000139:chemically induced* / Q000473:pathology
D065108:Ornithine Decarboxylase Inhibitors; D009952:Ornithine; D000518:Eflornithine