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Different methoxy indolalkylamines based on a common structure, and differing in the side chain attached at the 2 position of the indole ring were studied as MAO A inhibitors. Some are acetylenic derivatives and consequently might behave as "suicide" MAO inhibitors (FA 42, FA 43, FA 45). The rest of compounds are the corresponding parent amines and they might behave as MAO substrates (FA 51, FA 52, FA 53, FA 54). The kinetic behaviour of the parent amines as MAO A and MAO B inhibitors and substrates was determined. In case of acetylenic derivatives, kinetic constants defining the non-covalent adduct formation and the covalent adduct formation were also calculated for the mechanism-based inhibition. These parameters will allow us to establish the correlation with structural features that predetermine one compound to be a good MAO substrate or a good MAO A and MAO B inhibitor.

The subcellular distributions of amine oxidase activities MAO-A, MAO-B and SSAO, in bovine lung have been determined. MAO activities are largely confined to the mitochondria whereas SSAO activity is concentrated in the microsomal fraction. The contribution of different type of amine oxidase present in the microsomal fraction to the metabolism of the benzylamine, tyramine, phenylethylamine, tryptamine and dopamine were determined. The kinetic constants towards benzylamine showed SSAO to have a higher affinity than MAO-B, and the comparison of the Vmax/Km relationship for both enzymes indicated that benzylamine would be oxidised more efficiently by SSAO than by MAO-B.

Three different acetylenic analogues of tryptamine, in which the side chain is attached at the 2 position of the heterocyclic ring, were studied as inhibitors of MAO-A and MAO-B. IC50 values were determined after 30 min preincubation of the enzyme and inhibitor, at 37 degrees C before assay. Irreversibility and time-dependence of the inhibition were also established in each case. The kinetic parameters defining non-covalent complex formation and covalent adduct formation were calculated for the mechanism-based inhibition of both MAO-A and MAO-B by these compounds.