Inhibitory effects of the monoamine oxidase inhibitor tranylcypromine on the cytochrome P450 enzymes CYP2C19, CYP2C9, and CYP2D6.
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Salsali M, Holt A, Baker GB
Inhibitory effects of the monoamine oxidase inhibitor tranylcypromine on the cytochrome P450 enzymes CYP2C19, CYP2C9, and CYP2D6.
Cell Mol Neurobiol. 2004 Feb;24(1):63-76.
- PubMed ID
- 15049511 [ View in PubMed]
- Abstract
1. The inhibitory effects of tranylcypromine, a nonselective irreversible inhibitor of monoamine oxidase (MAO), on three cytochrome P450 (CYP) enzymes, namely CYP2C9, CYP2C19, and CYP2D6, have been evaluated in vitro. 2. The studies were conducted using cDNA-expressed human CYP enzymes and probe substrates. 3. A range of substrate concentrations was coincubated with a range of tranylcypromine concentrations in the presence of each of the CYP enzymes at 37 degrees C for a predetermined period of time. Product concentrations were quantified by HPLC with UV detection. 4. The results demonstrated that tranylcypromine is a competitive inhibitor of CYP2C19 (Ki = 32 microM) and CYP2D6 (Ki = 367 microM) and a noncompetitive inhibitor of CYP2C9 (Ki = 56 microM). 5. None of these inhibitory effects are considered clinically significant at usual therapeutic doses. However, in certain situations such as high dose tranylcypromine therapy, or in poor metabolizers of CYP2C19 substrates, clinically significant interactions might occur, particularly when tranylcypromine is coadministered with drugs with a narrow therapeutic index.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Tranylcypromine Amine oxidase [flavin-containing] A Protein Humans YesInhibitorDetails Tranylcypromine Amine oxidase [flavin-containing] B Protein Humans YesInhibitorDetails - Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Tranylcypromine Cytochrome P450 2C19 Protein Humans UnknownInhibitorDetails Tranylcypromine Cytochrome P450 2C9 Protein Humans UnknownInhibitorDetails Tranylcypromine Cytochrome P450 2D6 Protein Humans UnknownInhibitorDetails