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48197

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

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Last updated: 04 Jan 2025

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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. 

DOI

10.21608/blj.2016.48197

Keywords

Monoamine oxidase-A and-B (MAO-A& MAO -B), kinetics of inhibition, (S)-2-[4-(3-flourobenzyloxy)- benzylamino] propionamide, (FCE 26743), Inhibition Studies

Authors

First Name

Zakia Ben

Last Name

Ramadan

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Affiliation

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

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First Name

Keith

Last Name

Tipton

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Affiliation

Department of Biochemistry, Trinity College, Dublin 2, Ireland

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First Name

Safaa

Last Name

khater

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Affiliation

Department of Biochemistry, Zagazig University –Egypt.

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Volume

12

Article Issue

1

Related Issue

7422

Issue Date

2016-12-01

Receive Date

2016-10-19

Publish Date

2016-12-01

Page Start

259

Page End

274

Print ISSN

1687-4773

Online ISSN

2974-4725

Link

https://blj.journals.ekb.eg/article_48197.html

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https://blj.journals.ekb.eg/service?article_code=48197

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20

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Original Article

Type Code

988

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Journal

Publication Title

Biochemistry Letters

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https://blj.journals.ekb.eg/

MainTitle

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

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Article

Created At

22 Jan 2023