Inhibition of type A and B monoamine oxidase by 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinolines and their N-methylated derivatives |
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| Authors: | M Minami W Maruyama P Dostert T Nagatsu M Naoi |
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| Institution: | (1) Nagoya University School of Medicine, Nagoya, Japan;(2) Department of Neurology, Nagoya University School of Medicine, Nagoya, Japan;(3) Research and Development-Erbamont Group, Farmitalia Carlo Erba, Milan, Italy;(4) Division of Molecular Genetics (II) Neurochemistry, Institute of Comprehensive Medicine, School of Medicine, Fujita Health University, Aichi, Japan;(5) Present address: Department of Biosciences, Nagoya Institute of Technology, Nagoya, Japan |
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| Abstract: | Summary 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, andR enantiomers were more potent inhibitors thanS 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 K1 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. |
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| Keywords: | Type A and B monoamine oxidase inhibitors 6 7-dihydroxytetra-hydroisoquinolines salsolinols human brain synaptosomal mitochondria |
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