IN-VIVO HYDROXYLATION OF THE NEUROTOXIN, 1-METHYL-4-PHENYLPYRIDINIUM,AND THE EFFECT OF MONOAMINE-OXIDASE INHIBITORS - ELECTROSPRAY-MS ANALYSIS OF INTRASTRIATAL MICRODIALYSATES

The neurotoxin 1-methyl-4-phenylpyridinium (MPP(+)) has been shown to increase hydroxyl radical formation in the striatum. The production of hydroxyl radicals correlates with the MPP(+)-driven dopamine release which presumably leads to increased metabolism via monoamine oxidase o r increased dopamine autoxidation. Both processes result in enhanced p roduction of hydrogen peroxide, which in the presence of iron(II) ions decomposes to the hydroxyl radical. Monoamine oxidase inhibitors decr ease the production of hydroxyl radicals as measured by salicylate and 4-hydroxybenzoate trapping. As both MPP(+) and monoamine oxidase inhi bitors, such as deprenyl and MDL-72,974A, possess aromatic rings, hydr oxyl radical adduct formation was investigated in vitro in defined Fen ton systems and also in vivo using intra-striatal microdialysis to inf use MPP(+) to rats pretreated systemically with either deprenyl or MDL -72,974A. Electrospray mass spectrometric analysis, using full-scan, f ragment ion and constant neutral loss spectra, demonstrated ring hydro xylation of ail three compounds in the Fenton systems. Spectral compar ison of microdialysis samples with spectra from the Fenton reactions i ndicated the in vivo hydroxyl radical adduct attachment to MPP(+), dep renyl and possibly MDL-72,974A.