Studies of Monoamine Oxidase and Semicarbazide-Sensitive Amine Oxidase II. Inhibition by α-Methylated Substrate-Analogue Monoamines, α-Methyltryptamine, α-Methylbenzylamine and Two Enantiomers of α-Methylbenzylamine

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The α-methylated substrate-analogue monoamines, dl-α-methyltryptamine, dl-α-methylbenzylamine and two optical isomers of α-methylbenzylamine, were shown to be inhibitors of rat lung semicarbazide-sensitive amine oxidase (SSAO), with dl-α-methyltryptamine being the most potent and d-α-methylbenzylamine, the least. The three compounds, dl-α-methyltryptamine and the two isomers of α-methylbenzylamine also inhibited rat brain monoamine oxidase (MAO)-A and -B with a greater selectivity towards MAO-A. Preincubation of rat lung and brain homogenates with either of these compounds revealed that the inhibition of MAO and SSAO is reversible. The modes of inhibition of MAO-A and -B were competitive with the substrates tested. However, inhibition of SSAO by dl-α-methyltryptamine was found to be a mixed type (with a K<SUB>i</SUB> value of 47 μM) and those by the racemic form and two isomers of α-methylbenzylamine were non-competitive (with K<SUB>i</SUB> values of 90 μM for the racemic compound, 1070 μM for the d-isomer and 72 μM for the I-isomer). The present results indicate that SSAO can recognize optical isomers and that some α-methylated monoamines tested in the present study inhibit SSAO with properties different from those as MAO inhibitors.