INTERACTIONS OF MONOAMINE-OXIDASE INHIBITORS, N-ACETYLENIC ANALOGS OFTRYPTAMINE, WITH RAT-LIVER MICROSOMAL CYTOCHROME-P450

Interactions between some novel and potent monoamine oxidase inhibitor s (MAOIs), acetylenic analogues of tryptamine, and rat liver microsoma l cytochrome P450 (P450) as evidenced by visible spectra analysis were analysed. Compounds with a secondary aliphatic amine moiety throughou t induced type II difference spectra and exhibited the highest affinit y for P450, whereas tertiary amines induced type I spectral changes an d showed diminished affinity. P450 dependent aniline hydroxylase activ ity was inhibited by all compounds in an irreversible time-dependent m anner. Only tertiary aliphatic amines constituted the substrate for P4 50-dependent N-demethylase activity, with comparable kinetic parameter s. The N-demethylated metabolites were identified by thin-layer chroma tography and mass-spectrometric analyses. These findings describe the role of P450-dependent microsomal mono-oxygenase systems in the metabo lism of some MAOI acetylenic tryptamine derivatives and the possible h epatic contribution to adverse interactions between MAOIs, endobiotics and sympathomimetic compounds.