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.