caa a22 4500 477057381 CHVBK 20180405111350.0 cr unu---uuuuu 170330e19960601xx s 000 0 eng 10.1007/s002280050102 doi (NATIONALLICENCE)springer-10.1007/s002280050102 Methylene blue and the neurotoxic mechanisms of ifosfamide encephalopathy [Elektronische Daten] [A. Küpfer, C. Aeschlimann, T. Cerny] In cancer chemotherapy with ifosfamide the occurrence of a drug-related encephalopathy represents a severe adverse-effect of unknown origin. We found that the underlying mechanism resides in the mitochondrial toxicity of ifosfamide metabolites. The electron accepting drug methylene blue can substitute for the demonstrated flavoprotein deficiency and its administration leads to resolution of the encephalopathy in patients. The prophylactic administration of methylene blue is equally effective via another principal mechanism, namely oxidation of the excessive quantity of NADH formed during ifosfamide metabolism. The inhibition by methylene blue of multiple amine oxidase activities also prevents formation of the neurotoxic chloroacetaldehyde from ifosfamide-derived chloroethyl amine. Thus, methylene blue exhibits several synergistic modes of actions which enable the dose-limiting neurotoxicity of alkylating chemotherapy with ifosfamide in cancer patients to be overcome Springer-Verlag Berlin Heidelberg, 1996 Key words Ifosfamide nationallicence Neurotoxicity nationallicence Methylene blue nationallicence ketimines nationallicence mitochondrial drug toxicity nationallicence Küpfer A. Department of Clinical Pharmacology, University of Berne, Murtenstrasse 35, CH-3010 Berne, Switzerland, CH aut Aeschlimann C. Department of Clinical Pharmacology, University of Berne, Murtenstrasse 35, CH-3010 Berne, Switzerland, CH aut Cerny T. Department of Medical Oncology, University Hospital, Berne, Switzerland, CH aut https://doi.org/10.1007/s002280050102 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s002280050102 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Küpfer A. Department of Clinical Pharmacology, University of Berne, Murtenstrasse 35, CH-3010 Berne, Switzerland, CH aut NATIONALLICENCE 700 1- Aeschlimann C. Department of Clinical Pharmacology, University of Berne, Murtenstrasse 35, CH-3010 Berne, Switzerland, CH aut NATIONALLICENCE 700 1- Cerny T. Department of Medical Oncology, University Hospital, Berne, Switzerland, CH aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer