The biodisposition of MPP+ in mouse brain.
These studies assessed the role of biotransformation in the rapid elimination of MPP+ from the central nervous system (CNS) compartment of mice. Mice were given either MPP+ via the intracerebroventricular (i.c.v.) route, or MPTP intraperitoneally. The elimination of MPP+ from the brain over 10 h was similar in both groups and followed exponential kinetics. Using liquid scintillation counting, high-pressure liquid chromatography (HPLC) and gas chromatography/mass spectrometry (GC/MS) analysis, no compounds other than MPP+ were detected in brain 2-10 h after the i.c.v. administration of radiolabelled [14C/3H]MPP+. MPP+ was also unchanged after incubation with brain homogenates. These data indicate that MPP+ is not removed from the CNS compartment via biotransformation. Because of its positive charge and kinetics of elimination, the possibility of an active transport system is suggested.
Irwin
I
I
Institute for Medical Research, San Jose, CA 95128.
DeLanney
L E
LE
Di Monte
D
D
Langston
J W
JW
D015655:1-Methyl-4-phenylpyridinium; D000818:Animals; D001711:Biotransformation; D001921:Brain / Q000378:metabolism*; D006540:Herbicides / Q000493:pharmacokinetics; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D011726:Pyridinium Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*
D006540:Herbicides; D011726:Pyridinium Compounds; D015655:1-Methyl-4-phenylpyridinium