Interactions of Monoamine Oxidase from Human And Rat Liver Mitochondria with (S)-2-[4-(3-Flouro-Benzyloxy)-Benzylamino]-Propionamide

Document Type : Original Article

Authors

1 Department of Biochemistry, Faculty of Medicine University of Tripoli-Libya.

2 Department of Biochemistry, Trinity College, Dublin 2, Ireland

3 Department of Biochemistry, Zagazig University –Egypt.

Abstract

Background:The interactions of the anticonvulsant (S)-2-[4- (3-Flouro-Benzyloxy) Benzylamino]- Propionamide (FCE 26743) with MAO-A and MAO -B from human and rat liver mitochondria has been studied. Objective: This compound is an alanine derivative that differs from the parent anticonvulsant compound, 2-n-pentylamino acetamide in that alaninamide residue replaces the glycinamide moiety, and in the presence of a phenyl ring substituted in the para-position by a 3-flouro-benzyloxy group. Results: The results indicated that, The Ki values for rat and human MAO-A were > 1000 times higher than their corresponding values for rat and human MAO-Consistent with the IC50values that showed this compound to be > 1000 times more potent as an inhibitor of MAO-B than of MAO-A of the same species. There was an increase in the strength of inhibition when MAO-B was incubated with this compound. This was confirmed by the extended time-courses studies which showed a rather rapid increase in the degree of inhibition of MAO-B, despite incubation being continued for a total of 4h. This is consistent with FCE 26743 being a reversible inhibitor for MAO-A and a slow- binding reversible inhibitor of MAO-B.FCE 26743 was found to be a time-independent weak inhibitor of MAO-A from both rat and human preparations. However, there was a significant difference in the inhibitory potency of FCE 26743 with MAO-B from the two species, the Ki value for rat MAO-B was about two times higher than that for human MAOB. Conclusion: The FCE 26743 was not metabolized (in vitro) by either human or rat liver mitochondrial MAO-A or -B. Without enzyme-inhibitor preincubation FCE 26743 was found to be a competitive inhibitor of both MAO-A and MAO-B from rat and human liver mitochondria. 

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