Designer drugs that are potent inhibitors of CYP2D6

J Clin Psychopharmacol. 2002 Jun;22(3):330-2. doi: 10.1097/00004714-200206000-00015.


Some abused drugs are substrates of CYP2D6 (e.g., paramethoxyamphetamine, methylenedioxy-methamphetamine). CYP2D6 inhibition by concurrently used drugs of abuse could potentiate such drugs and increase acute toxicity. Ten designer drugs were tested as inhibitors of CYP2D6. Only 1-methyl-4-phenyl-4-propionoxypiperidine (MPPP) and 1-[2-phenylethyl]-4-phenyl-4-acetoxypiperidine (PEPAP) interacted significantly (Ki 1.6 microM and 0.3 microM, respectively). Both are synthetic analogues of meperidine sold as "synthetic heroin." No CYP2D6-mediated metabolites were detected for either compound. Concurrent oral use of CYP2D6 substrates with MPPP and PEPAP may represent a kinetic drug interaction risk, but this risk must be confirmed clinically.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cytochrome P-450 CYP2D6 / metabolism
  • Cytochrome P-450 CYP2D6 Inhibitors*
  • Designer Drugs / pharmacokinetics
  • Designer Drugs / pharmacology*
  • Enzyme Inhibitors / pharmacokinetics
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / enzymology


  • Cytochrome P-450 CYP2D6 Inhibitors
  • Designer Drugs
  • Enzyme Inhibitors
  • Cytochrome P-450 CYP2D6