Inhibition of type A and B monoamine oxidase by 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinolines and their N-methylated derivatives.
6,7-Dihydroxy-1,2,3,4-tetrahydroisoquinoline (norsalsolinol) and 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (salsolinol), and their N-methylated derivatives were found to inhibit type A and B monoamine oxidase isolated from human brain synaptosomal mitochondria. 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, and their Ki values were much higher than those to type A. Types of inhibition of type A monoamine oxidase depended on the enzyme sources. Inhibition of monoamine oxidase by 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinolines is discussed in relation to their chemical structures.
Minami
M
M
Nagoya University School of Medicine, Japan.
Maruyama
W
W
Dostert
P
P
Nagatsu
T
T
Naoi
M
M
D001921:Brain / Q000187:drug effects / Q000201:enzymology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology*; D007700:Kinetics; D007735:Kynuramine / Q000378:metabolism; D008745:Methylation; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010920:Placenta / Q000187:drug effects / Q000201:enzymology; D011247:Pregnancy; D012490:Salsoline Alkaloids / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013574:Synaptosomes / Q000187:drug effects / Q000201:enzymology
D007546:Isoquinolines; D008996:Monoamine Oxidase Inhibitors; D012490:Salsoline Alkaloids; D007735:Kynuramine; C036617:salsolinol; C020784:norsalsolinol; D008995:Monoamine Oxidase