title: Studies of monoamine oxidase and semicarbazide-sensitive amine oxidase. II. Inhibition by alpha-methylated substrate-analogue monoamines, alpha-methyltryptamine, alpha-methylbenzylamine and two enantiomers of alpha-methylbenzylamine.
abstract: The alpha-methylated substrate-analogue monoamines, dl-alpha-methyltryptamine, dl-alpha-methylbenzylamine and two optical isomers of alpha-methylbenzylamine, were shown to be inhibitors of rat lung semicarbazide-sensitive amine oxidase (SSAO), with dl-alpha-methyltryptamine being the most potent and d-alpha-methylbenzylamine, the least. The three compounds, dl-alpha-methyltryptamine and the two isomers of alpha-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-alpha-methyltryptamine was found to be a mixed type (with a Ki value of 47 microM) and those by the racemic form and two isomers of alpha-methylbenzylamine were non-competitive (with Ki values of 90 microM for the racemic compound, 1070 microM for the d-isomer and 72 microM for the l-isomer). The present results indicate that SSAO can recognize optical isomers and that some alpha-methylated monoamines tested in the present study inhibit SSAO with properties different from those as MAO inhibitors.
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology; D007700:Kinetics; D008168:Lung / Q000201:enzymology; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010627:Phenethylamines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012663:Semicarbazides / Q000494:pharmacology*; D013237:Stereoisomerism; D014363:Tryptamines / Q000494:pharmacology*
chemical_list: D008996:Monoamine Oxidase Inhibitors; D010627:Phenethylamines; D012663:Semicarbazides; D014363:Tryptamines; C015293:indopan; C033198:1-phenethylamine