Phentermine inhibition of recombinant human liver monoamine oxidases A and B

Biochemical Pharmacology
R K NandigamaD E Edmondson

Abstract

Recent studies with rat tissue preparations have suggested that the anorectic drug phentermine inhibits serotonin degradation by inhibition of monoamine oxidase (MAO) A with a K(I) value of 85-88 microM, a potency suggested to be similar to that of other reversible MAO inhibitors (Ulus et al., Biochem Pharmacol 2000;59:1611-21). Since there are known differences between rats and humans in substrate and inhibitor specificities of MAOs, the interactions of phentermine with recombinant human purified preparations of MAO A and MAO B were determined. Human MAO A was competitively inhibited by phentermine with a K(I) value of 498+/-60 microM, a value approximately 6-fold weaker than that observed for the rat enzyme. Phentermine was also observed to be a competitive inhibitor of recombinant human liver MAO B with a K(I) value of 375+/-42 microM, a value similar to that observed with the rat enzyme (310-416 microM). In contrast to the behavior with rat tissue preparations, no slow time-dependent behavior was observed for phentermine inhibition of purified soluble human MAO preparations. Difference absorption spectral studies showed similar perturbations of the covalent FAD moieties of both human MAO A and MAO B, which suggests a simila...Continue Reading

Citations

Mar 30, 2007·Journal of Neural Transmission·F Cruz, D E Edmondson
Jun 12, 2003·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Amal KaddoumiKenichiro Nakashima
Sep 1, 2005·Proceedings of the National Academy of Sciences of the United States of America·Luigi De ColibusAndrea Mattevi
Oct 28, 2009·The American Journal of Emergency Medicine·Richard B Rothman, Ed J Hendricks
Feb 11, 2020·Frontiers in Pharmacology·Miguel Reyes-ParadaBruce K Cassels

❮ Previous
Next ❯

Related Concepts

Related Feeds

Anorexia Nervosa

Anorexia nervosa (AN) is a psychiatric condition characterized by severe weight loss and secondary problems associated with malnutrition. Here is the latest research on AN.