Phentermine inhibition of recombinant human liver monoamine oxidases A and B.
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Nandigama RK, Newton-Vinson P, Edmondson DE
Phentermine inhibition of recombinant human liver monoamine oxidases A and B.
Biochem Pharmacol. 2002 Mar 1;63(5):865-9.
- PubMed ID
- 11911838 [ View in PubMed]
- 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 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.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Phentermine Amine oxidase [flavin-containing] A Protein Humans YesAntagonistDetails Phentermine Amine oxidase [flavin-containing] B Protein Humans YesAntagonistDetails