M NAOI, W MARUYAMA, M MINAMI, P DOSTERT, SH PARVEZ, T NAGATSU
BIOGENIC AMINES 9(5-6) 367-379 1993年 査読有り
The effects of naturally occurring tetrahydroisoquinolines on monoamine catabolism were examined by in vivo microdialysis study in the rat striatum, or by in vitro experiments using human brain synaptosomes as enzyme samples. By in vivo experiment, catechol isoquinolines, (R) and (S) enantiomer of 1-methyl- and 2-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (salsolinol and N-methyl-norsalsolinol) markedly inhibited oxidation of serotonin by type A oxidase. On the other band, isoquinolines without catechol, 1,2,3,4-tetrabydroisoquinoline, 1-methyl-derivative and N-methyl-isoquinolinium ion, mainly inhibited dopamine metabolism by the oxidase.
By in vitro experiments, norsalsolinol and salsolinol, and their N-methylated derivatives were found to inhibit monoamine oxidase. N-Methyl-norsalsolinol, (R) and (S) enantiomer of salsolinol, and N-methyl-salsolinols inhibited type A monoamine oxidase competitively to the substrate, kynuramine, and R enantiomers were more potent inhibitors than S enantiomers. The inhibition was reversible. Norsalsolinol induced positive cooperativity toward kynuramine. Both norsalsolinol and N-methyl-norsalsolinol inhibited type B oxidase non-competitively to the substrate, but their K(i) values were much higher than those to type A.
These results are discussed in relation to possible involvement of the isoquinolines as neuro-toxic and neuro-protective agents to the pathogenesis of some neuro-degenerative diseases, such as Parkinson's disease, or to clinical features of some diseases, such as alcoholism.