The Effect of the anticonvulsant (S)-2-[4-(3-Flouro-Benzyloxy) Benzylamino]- Propionamide on Monoamine Oxidase (A&B)

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 Central Lab, Faculty of Vet. Med.,Zagagazig University, Egypt

Abstract

The effect of the potent anticonvulsant the alanine derivative (S)-2-[4-(3-flourobenzyloxy)-benzylamino] propionamide (FCE 26743) on MAO-B from ox liver mitochondria and human platelets and MAO-A & –B from Human brain mitochondria has been studied. This compound involves replacement of glycinamide of the parent (2-n-pentylamino acetamide) compound with alanine and replacement of the pentyl moiety with a phenyl ring substituted in the para-position by a 3-flouro-benzyloxy group. (FCE 26743) was not metabolized to any extent by either form of the enzyme from any of the preparations used. For human brain mitochondrial MAO-A and –B In the absence of preincubation, FCE 26743 was found to be a competitive inhibitor with the IC50 values of approx 80 μM and 0.26 ± 0.024 μM respectively. This showed FCE 26743 to be > 300 times more potent as an inhibitor of MAO-B than of MAO-A. After preincubation with FCE 26743 for 30 min at 37oC, no significant time-dependent inhibition of human brain MAO-A was found. However the degree of inhibition of MAO-B increased significantly. This was confirmed by the extended time-courses studies which showed a rather rapid increase in the degree of inhibition of MAO-B. The IC50 values for the inhibition of 5-HT and PEA oxidation after preincubation were > 80 μM and 0.079 ± 0.009 μM, for human brain MAO-A and -B, respectively FCE 26743 inhibited human platelet MAO-B before incubation with IC50 value of 0.16 ± 0.023 μM and after preincubation of FCE 26743 and the enzyme at 37oC for 30 min the IC50 value was 0.064 ± 0.014 μM. The inhibition studies with ox liver mitochondrial MAO-B indicated that without enzyme-inhibitor preincubation, the inhibition of this form of the enzyme was also competitive and shows that FCE 26743 is > 500-times more potent inhibitor for human brain MAO-B than for ox liver MAO-B. Furthermore, MAO-B from ox liver showed little or no significant time-dependent inhibition by this compound. 

Keywords

Files

Share

How to cite

Statistics