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N‐Methylation of Dopamine‐Derived 6,7‐Dihydroxy‐1,2,3,4‐Tetrahydroisoquinoline, (R)‐Salsolinol, in Rat Brains: In Vivo Microdialysis Study
Author(s) -
Maruyama Wakako,
Nakahara Daiichiro,
Ota Miyuki,
Takahashi Tsutomu,
Takahashi Akira,
Nagatsu Toshiharu,
Naoi Makoto
Publication year - 1992
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 - 10.1111/j.1471-4159.1992.tb09384.x
Subject(s) - substantia nigra , dopaminergic , dopamine , tetrahydroisoquinoline , microdialysis , striatum , neurotoxin , chemistry , in vivo , mptp , pharmacology , neurotoxicity , biochemistry , biology , endocrinology , toxicity , stereochemistry , microbiology and biotechnology , organic chemistry
N ‐Methylation of ( R )‐1‐methyl‐6,7‐dihydroxy‐1,2,3,4‐tetrahydroisoquinoline [( R )‐salsolinol] derived from dopamine was proved by in vivo microdialysis study in the rat brain. The striatum was perfused with ( R )‐salsolinol and N‐methylated compound was identified in the dialysate using HPLC and electrochemical detection with multichanneled electrodes. N ‐Methylation of ( R )‐salsolinol was confirmed in three other regions of the brain, the substantia nigra, hypothalamus, and hippocampus. In the substantia nigra, the amount of N ‐methylated ( R )‐salsolinol was significantly larger than in the other three regions. These results indicate that around dopaminergic neurons, particularly in the substantia nigra, ( R )‐salsolinol was methylated into N ‐methyl‐( R )‐salsolinol, which has a chemical structure similar to that of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine, the selective dopaminergic neurotoxin. N ‐Methylation of tetrahydroisoquinolines and β‐carbolines have already been proven to increase their toxicity to dopaminergic neurons and N ‐methylation might be an essential step for these alkaloids to increase their toxicity. On the other hand, after perfusion of ( R )‐salsolinol, release of dopamine and 5‐hydroxytryptamine was observed and inhibition of monoamine oxidase was indicated. ( R )‐Salsolinol and its derivatives may be candidates for being dopaminergic neurotoxins.