Dopamine-derived 1-methyl-6,7-dihydroxyisoquinolines as hydroxyl radical promoters and scavengers in the rat brain: in vivo and in vitro studies.
The effects of derivatives of dopamine-derived isoquinoline, (R)-1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline [or (R)-salsolinol] on hydroxyl radical production were studied in vivo and in vitro. As reported previously, (R)-salsolinol is N-methylated in the brain into N-methyl-(R)-salsolinol, which is further oxidized into the 1,2-dimethyl-6,7-dihydroxyisoquinolinium ion. Using in vivo microdialysis, we measured hydroxyl radical levels in the rat striatum by HPLC after derivatization to 2,3-dihydroxybenzoic acid with salicylic acid. (R)-Salsolinol and the isoquinolinium ion (40 and 200 microM) and N-methyl-(R)-salsolinol (200 microM) reduced in vivo radical formation, with reduction of dopamine catabolism. (R)-Salsolinol and the isoquinolinium ion reduced in vitro hydroxyl radical production from dopamine autoxidation. On the other hand, 40 microM N-methyl-(R)-salsolinol increased the hydroxyl radical level in the striatum, and the radical production by its autoxidation was confirmed in vitro. N-Methyl-(R)-salsolinol affected neither in vivo dopamine catabolism nor in vitro production of hydroxyl radicals from dopamine. These results show that (R)-salsolinol and N-methyl-(R)-salsolinol may be neuroprotective and neurotoxic, respectively, and thus might be in the pathogenesis of Parkinson's disease.
Maruyama
W
W
Department of Neurology, Nagoya University School of Medicine, Japan.
Dostert
P
P
Naoi
M
M
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000031:analogs & derivatives* / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology*; D017665:Hydroxyl Radical / Q000378:metabolism*; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D044005:Tetrahydroisoquinolines
D016166:Free Radical Scavengers; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D017665:Hydroxyl Radical; C069194:2-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline; D008995:Monoamine Oxidase; D004298:Dopamine