Interactions of Monoamine Oxidase Inhibitors,N-Acetylenic Analogues of Tryptamine,with Rat Liver Microsomal Cytochrome P450

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.     

Chromatography of Red Cell Hemolysate

Column chromatography on DEAE-cellulose has been used to fractionatered cell homolysates. Under the experimental conditions described above,hemoglobin is not bound to the column and is eluted by the starting buffer.Upon gradient salt elution other proteins are fractionated in a number ofpeaks. Some enzyme activities were localized in the chromatograms; acidphosphatase appeared in three distinct chromatographic forms with differentenzymatic properties.

Submitted on December 19, 1961 Accepted on March 29, 1962     

Multiform Ventricular Ectopic Rhythm by Combined Parasystolic and Reentrant Activities

Multiform ventricular ectopic rhythm (MVER), i.e., at least two QRS configurations of ventricular ectopic beats (VEBs), was assessed by 24-hour ambulatory ECG recording in four patients with ventricular parasystole (VP). In two of these four patients, VEBs with fixed coupling to the preceding impulses coexisted with VP beats of different configuration. In case no. 1, the VEBs had an identical coupling interval to sinus bents and VP beats, suggesting a mechanism of reentry elicited from both dominant pacemakers. In case no. 2, an intermittent form of VP due to type II second-degree entrance block was present. In this patient, the VEBs were coupled to sinus beats and to sinus-VP fusion beats and appeared to be dependent on the sinus beats reaching the VP focus. A mechanism of reentry determined by the penetration of sinus beats into the VP area, with prematurity-dependent aberrancy of VEBs, was suggested for the coupled VEBs in this patient. These observations suggest that the coexistence of an automatic ventricular ectopic focus and of a reentrant activity determined by, or elicited from, an area of automaticity may constitute the underlying mechanism of MVER in some patients.