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Dopamine‐Derived 1‐Methyl‐6,7‐Dihydroxyisoquinolines as Hydroxyl Radical Promoters and Scavengers in the Rat Brain: In Vivo and In Vitro Studies
Author(s) -
Maruyama Wakako,
Dostert Philippe,
Naoi Makoto
Publication year - 1995
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1995.64062635.x
Subject(s) - chemistry , hydroxyl radical , in vivo , dopamine , autoxidation , microdialysis , methyl radical , in vitro , biochemistry , radical , biology , extracellular , endocrinology , microbiology and biotechnology
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 µ M ) and N ‐methyl‐( R )‐salsolinol (200 µ M ) 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 µ M 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 involved in the pathogenesis of Parkinson's disease.