The Effect of the anticonvulsant (S)-2-[4-(3-Flouro-Benzyloxy) Benzylamino]- Propionamide on Monoamine Oxidase (A&B) | ||||
| Biochemistry Letters | ||||
| Article 10, Volume 12, Issue 1, 2016, Page 102-114 PDF (613.49 K) | ||||
| Document Type: Original Article | ||||
| DOI: 10.21608/blj.2016.47872 | ||||
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| Authors | ||||
| Zakia M. Ben Ramadan1; Keith F. Tipton2; Maha M. El Deib3 | ||||
| 1Department of Biochemistry, Faculty of Medicine University of Tripoli-Libya | ||||
| 2Department of Biochemistry, Trinity College, Dublin 2, Ireland | ||||
| 3Central 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 | ||||
| Monoamine oxidase- A and-B (MAO-A&-B); kinetics of inhibition; (S)-2-[4-(3- flourobenzyloxy)-benzylamino] propionamide; (FCE 26743); Inhibition Studies | ||||
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