Amsacrine

Abstract The synthetic aminoacridine, amsacrine (AMSA, m-AMSA), is used as an antitumor agent, since it intercalates into DNA and inhibits nuclear and mitochondrial topoisomerase II in mammals (8). The enzyme is inhibited because amsacrine induces a covalent attachment of topoisomerase to both strands of the double helix by stabilizing the cleavable complex, a reaction intermediate. m-AMSA, like cisplatin and mitomycin C, inhibits ubiquitin-adenosine triphosphate (ATP)-dependent proteolysis (4). The related compound o AMSA is ineffective as a cancer treatment. The blood-brain barrier severely limits the entry of intra venously administered m-AMSA into cerebrospinal fluid (CSF) (1). After direct intraventricular administration, m-AMSA had a CSF half-life of only 115 min and clinical neurotoxic effects were not observed. Histopathological studies were not performed. Generalized seizures accomparried treatment with amsacrine in a few patients (6,7,9). Single lethal doses of m-AMSA cause ataxia and seizures in dogs and monkeys (3). Other observations on neurological manifestations, such as peripheral neuropathy (2,5), are likely unrelated to m-AMSA.