Designer drugs that are potent inhibitors of CYP2D6.
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.
Pritzker
David
D
Department of Pharmacology, University of Toronto, Canada.
Kanungo
Anish
A
Kilicarslan
Tansel
T
Tyndale
Rachel F
RF
Sellers
Edward M
EM
D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D015198:Designer Drugs / Q000493:pharmacokinetics / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology
D065690:Cytochrome P-450 CYP2D6 Inhibitors; D015198:Designer Drugs; D004791:Enzyme Inhibitors; D019389:Cytochrome P-450 CYP2D6