The kinetics of monoamine oxidase inhibition by three 2-indolylmethylamine derivatives.
The inhibition of bovine brain mitochondrial MAO-A and MAO-B by three acetylenic and non-acetylenic derivatives of 2-indolylmethylamine, chosen among more than 100 new compounds, were studied. The non-acetylenic derivative N-methyl-2(5-hydroxy-1-methylindolyl)methylamine (1) was a weak non-selective inhibitor which was shown to act in a reversible and competitive manner towards the deamination of tyramine. The two acetylenic derivatives N-methyl-N-(2-propynyl)-2-(5-benzyloxy-1-methylindolyl)methylamine (2) and N-methyl-N-(2-propynyl)-2-(5-hydroxy-1-methylindolyl)methylamine (3) were potent MAO inhibitors, one of them non-selective (compound 2) and the other MAO-A selective inhibitor (compound 3). Both of them were irreversible and competitive inhibitors, compound 2 towards the deamination of tyramine and compound 3 towards the deamination of serotonin and beta-phenylethylamine. A mechanism for the inhibition of the enzyme by both irreversible inhibitors is proposed and the inhibition parameters are determined.
Cruces
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Instituto de Química Orgánica General del CSIC, Madrid, Spain.
Elorriaga
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Fernández-Alvarez
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D000480:Alkynes / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D001921:Brain / Q000201:enzymology; D002417:Cattle; D007211:Indoles / Q000494:pharmacology*; D007700:Kinetics; D008744:Methylamines / Q000494:pharmacology*; D008928:Mitochondria / Q000201:enzymology; D015394:Molecular Structure; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010627:Phenethylamines / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D014439:Tyramine / Q000378:metabolism
D000480:Alkynes; D007211:Indoles; D008744:Methylamines; D008996:Monoamine Oxidase Inhibitors; D010627:Phenethylamines; C065187:N-methyl-N-(2-propynyl)-2-(5-benzyloxy-1-methylindolyl)methylamine; C065188:N-methyl-N-(2-propynyl)-2-(5-hydroxy-1-methylindolyl)methylamine; C029261:phenethylamine; D012701:Serotonin; D008995:Monoamine Oxidase; D014439:Tyramine