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

Abstract

AbstractThe α-methylated substrate-analogue monoamines, dl-α-methyltryp-tamine. 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-methyl-benzylamine, 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-ॅ. 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 K1 value of 47 μM) and those by the racemic form and two isomers of α-methylbenzylamine were noncompetitive (with K1 values of 90 μM for the racemic compound, 1070 μM for the d-isomer and 72 μM for the l-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.