INHIBITION OF MONOAMINE-OXIDASE FROM BOVINE RETINA BY BETA-CARBOLINES

The behaviour of some beta-carboline derivatives as inhibitors of mono amine oxidase has been studied in bovine retina. Inhibition was found not to show any significant time dependence. Di- and tetrahydro-beta-c arbolines were shown to behave as reversible and competitive inhibitor s. In contrast, the fully unsaturated beta-carbolines harmane, harmine and harmaline, which showed deviation from linearity at high substrat e concentrations, behaved as tight-binding inhibitors. In these cases, the concentration of the enzyme and the inhibitor were of the same or der. This was confirmed by the K-i values for these compounds in the n anomolar concentration range. Consistent with this was that inhibition was only partly reversed by dialysis for 18 h at 4 degrees C, althoug h complete reversal was observed after dialysis for the same period at 37 degrees C. Structure-activity relationships indicated that substit ution of a methoxy group at the C7 position of the aromatic ring is de terminant for this tight-binding behaviour; a substitution of this gro up at the C6 position greatly reduced inhibition. Since beta-carboline s have been reported to be formed endogenously, this suggests that the y might have important physiological actions on monoamine oxidase acti vity in-vivo. In contrast, all the beta-carbolines investigated in thi s study had low potencies as inhibitors of monoamine oxidase B.