Ravi K Nandigama, Paige Newton-Vinson, Dale E Edmondson
Department of Biochemistry, Emory University School of Medicine, Rollins Research Building, 1510 Clifton Road, Atlanta, GA 30322-3050, USA.
Biochemical pharmacology 2002 Mar 1Recent 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 similar mode of binding in both enzymes. These data suggest that phentermine inhibition of human MAO A (or of MAO B) is too weak to be of pharmacological relevance.
Ravi K Nandigama, Paige Newton-Vinson, Dale E Edmondson. Phentermine inhibition of recombinant human liver monoamine oxidases A and B. Biochemical pharmacology. 2002 Mar 1;63(5):865-9
PMID: 11911838
View Full Text