Inhibition of dextromethorphan metabolism by moclobemide

Psychopharmacology (Berl). 1998 Jan;135(1):22-6. doi: 10.1007/s002130050481.


This pilot study was conducted to evaluate the potential of the new antidepressant moclobemide to inhibit the cytochrome enzyme P4502D6 (CYP2D6) using the cough suppressant dextromethorphan as a substrate in four extensive metabolizers (EM) of debrisoquine. The subjects received seven oral doses of 20 mg dextromethorphan at 4-h intervals over 2 days (1 and 2) and subsequently moclobemide (300 mg b.i.d.) for 9 days. On days 10 and 11, they received seven doses of 20 mg dextromethorphan in addition to moclobemide. During monotreatment and combined treatment, blood was collected on days 2 and 11, respectively, for determination of dextromethorphan and its demethylated metabolites using automated high-performance liquid chromatography with column switching. Concurrent administration of moclobemide markedly reduced the O-demethylation of dextromethorphan, whereas the N-demethylation of dextrorphan to hydroxymorphinan was not affected. The findings indicate that moclobemide can affect the pharmacokinetics of drugs that are mainly metabolized by CYP2D6.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Antidepressive Agents / pharmacology*
  • Area Under Curve
  • Benzamides / pharmacology*
  • Biotransformation
  • Dextromethorphan / pharmacokinetics*
  • Drug Interactions
  • Humans
  • Moclobemide
  • Monoamine Oxidase Inhibitors / pharmacology*


  • Antidepressive Agents
  • Benzamides
  • Monoamine Oxidase Inhibitors
  • Dextromethorphan
  • Moclobemide