RT Journal Article
SR Electronic
T1 Inhibition of (mono)amine oxidase activity and prevention of ifosfamide encephalopathy by methylene blue.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 1336
OP 1339
VO 24
IS 12
A1 C Aeschlimann
A1 T Cerny
A1 A Küpfer
YR 1996
UL http://dmd.aspetjournals.org/content/24/12/1336.abstract
AB The clinical application of ifosfamide is hampered by a central nervous side effect, the so-called ifosfamide encephalopathy. Methylene blue is effective in prophylaxis and reversal of this side effect. In the present study, the in vitro inhibition of (mono)amine oxidases by methylene blue is demonstrated in two different experimental systems. The results provide an explanation for the preventive action of methylene blue in ifosfamide neurotoxicity, because the generation of chloroacetaldehyde (a potential neurotoxin of ifosfamide metabolism) is prevented in liver mitochondria and extrahepatic tissues. Generation of alkylating metabolites was also studied in rat liver perfusions, and methylene blue did not show any inhibition of ifosfamide activation. From these data, we conclude that the clinical effectiveness of methylene blue in treatment and prevention of ifosfamide encephalopathy might be based on inhibition of (mono)amine oxidases. Hepatic bioactivation of ifosfamide is not influenced by methylene blue.