Characterization of phentermine and related compounds as monoamine oxidase (MAO) inhibitors.

Article Details

Citation

Ulus IH, Maher TJ, Wurtman RJ

Characterization of phentermine and related compounds as monoamine oxidase (MAO) inhibitors.

Biochem Pharmacol. 2000 Jun 15;59(12):1611-21.

PubMed ID
10799660 [ View in PubMed
]
Abstract

Phentermine was shown in the 1970s to inhibit the metabolism of serotonin by monoamine oxidase (MAO), but never was labeled as an MAO inhibitor; hence, it was widely used in combination with fenfluramine, and continues to be used, in violation of their labels, with other serotonin uptake blockers. We examined the effects of phentermine and several other unlabeled MAO inhibitors on MAO activities in rat lung, brain, and liver, and also the interactions of such drugs when administered together. Rat tissues were assayed for MAO-A and -B, using serotonin and beta-phenylethylamine as substrates. Phentermine inhibited serotonin-metabolizing (MAO-A) activity in all three tissues with K(i) values of 85-88 microM. These potencies were similar to those of the antidepressant MAO inhibitors iproniazid and moclobemide. When phentermine was mixed with other unlabeled reversible MAO inhibitors (e.g. pseudoephedrine, ephedrine, norephedrine; estradiol benzoate), the degree of MAO inhibition was additive. The cardiac valvular lesions and primary pulmonary hypertension that have been reported to be associated with fenfluramine-phentermine use may have resulted from the intermittent concurrent blockage of both serotonin uptake and metabolism.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
Ephedra sinica rootAmine oxidase [flavin-containing] AProteinHumans
Yes
Inhibitor
Details
Ephedra sinica rootAmine oxidase [flavin-containing] BProteinHumans
Yes
Inhibitor
Details
MetamfetamineAmine oxidase [flavin-containing] AProteinHumans
Yes
Inhibitor
Details
MetamfetamineAmine oxidase [flavin-containing] BProteinHumans
Yes
Inhibitor
Details
PhentermineAmine oxidase [flavin-containing] AProteinHumans
Yes
Antagonist
Details
PhentermineAmine oxidase [flavin-containing] BProteinHumans
Yes
Antagonist
Details
Drug Enzymes
DrugEnzymeKindOrganismPharmacological ActionActions
PseudoephedrineAmine oxidase [flavin-containing] AProteinHumans
Unknown
Inhibitor
Details