TY - JOUR
T1 - Interactions of Monoamine Oxidase Inhibitors, N‐Acetylenic Analogues of Tryptamine, with Rat Liver Microsomal Cytochrome P450
AU - VALOTI, MASSIMO
AU - COSTANZO, MARISA
AU - SGARAGLI, GIAN PIETRO
AU - PEREZ, VIRGILI
AU - FERNANDEZ‐ALVAREZ, ELDIBERTO
AU - UNZETA, MERCEDES
PY - 1994/1/1
Y1 - 1994/1/1
N2 - Abstract— Interactions between some novel and potent monoamine oxidase inhibitors (MAOIs), acetylenic analogues of tryptamine, and rat liver microsomal cytochrome P450 (P450) as evidenced by visible spectra analysis were analysed. Compounds with a secondary aliphatic amine moiety throughout induced type II difference spectra and exhibited the highest affinity for P450, whereas tertiary amines induced type I spectral changes and showed diminished affinity. P450 dependent aniline hydroxylase activity was inhibited by all compounds in an irreversible time‐dependent manner. Only tertiary aliphatic amines constituted the substrate for P450‐dependent N‐demethylase activity, with comparable kinetic parameters. The N‐demethylated metabolites were identified by thin‐layer chromatography and mass‐spectrometric analyses. These findings describe the role of P450‐dependent microsomal mono‐oxygenase systems in the metabolism of some MAOI acetylenic tryptamine derivatives and the possible hepatic contribution to adverse interactions between MAOIs, endobiotics and sympathomimetic compounds. 1994 Royal Pharmaceutical Society of Great Britain
AB - Abstract— Interactions between some novel and potent monoamine oxidase inhibitors (MAOIs), acetylenic analogues of tryptamine, and rat liver microsomal cytochrome P450 (P450) as evidenced by visible spectra analysis were analysed. Compounds with a secondary aliphatic amine moiety throughout induced type II difference spectra and exhibited the highest affinity for P450, whereas tertiary amines induced type I spectral changes and showed diminished affinity. P450 dependent aniline hydroxylase activity was inhibited by all compounds in an irreversible time‐dependent manner. Only tertiary aliphatic amines constituted the substrate for P450‐dependent N‐demethylase activity, with comparable kinetic parameters. The N‐demethylated metabolites were identified by thin‐layer chromatography and mass‐spectrometric analyses. These findings describe the role of P450‐dependent microsomal mono‐oxygenase systems in the metabolism of some MAOI acetylenic tryptamine derivatives and the possible hepatic contribution to adverse interactions between MAOIs, endobiotics and sympathomimetic compounds. 1994 Royal Pharmaceutical Society of Great Britain
U2 - 10.1111/j.2042-7158.1994.tb03813.x
DO - 10.1111/j.2042-7158.1994.tb03813.x
M3 - Article
VL - 46
SP - 360
EP - 365
JO - Journal of Pharmacy and Pharmacology
JF - Journal of Pharmacy and Pharmacology
SN - 0022-3573
IS - 5
ER -