Inactivation of human liver cytochrome P-450 by the drug methoxsalen and other psoralen derivatives

Biochem Pharmacol. 1987 Mar 15;36(6):951-5. doi: 10.1016/0006-2952(87)90190-0.


The effects of psoralen derivatives on cytochrome P-450 have been studied in human liver microsomes. CO-binding cytochrome P-450 was decreased by 33% after 10 min of incubation with 1.5 mM EDTA, an NADPH-regenerating system and 20 microM methoxsalen (8-methoxypsoralen). No destruction of cytochrome P-450 was observed when either NADPH or methoxsalen was omitted. A similar (27%) decrease in CO-binding required a 100-times higher concentration of allylisopropylacetamide (2 mM). The activities of 7-ethoxycoumarin deethylase and benzo(a)pyrene hydroxylase were decreased by about 50% in the presence of 12.5 microM methoxsalen. At this low concentration, neither cimetidine nor SKF 525-A or piperonyl butoxide had any significant inhibitory effect. Monooxygenase activities were also decreased in the presence of 12.5 microM bergapten (5-methoxypsoralen) or 12.5 microM psoralen, but not with 12.5 microM trioxsalen (trimethylpsoralen). CO-binding cytochrome P-450 was not decreased after 10 min of incubation with 1.5 mM EDTA, an NADPH-regenerating system and 20 microM trioxsalen. We conclude that methoxsalen is an extremely potent suicide inhibitor of cytochrome P-450 in human liver microsomes. Bergapten and psoralen are also inhibitory whereas trioxsalen has little effects. In the latter derivative, a methyl group is attached on the furan ring and may hinder its metabolic activation and the inactivation of cytochrome P-450.

MeSH terms

  • 5-Methoxypsoralen
  • 7-Alkoxycoumarin O-Dealkylase
  • Benzopyrene Hydroxylase / antagonists & inhibitors
  • Carbon Monoxide / metabolism
  • Cytochrome P-450 Enzyme Inhibitors*
  • Ficusin / pharmacology
  • Furocoumarins / pharmacology*
  • Humans
  • Methoxsalen / pharmacology*
  • Microsomes, Liver / enzymology*
  • Oxygenases / antagonists & inhibitors
  • Trioxsalen / pharmacology


  • Cytochrome P-450 Enzyme Inhibitors
  • Furocoumarins
  • 5-Methoxypsoralen
  • Carbon Monoxide
  • Oxygenases
  • 7-Alkoxycoumarin O-Dealkylase
  • Benzopyrene Hydroxylase
  • Ficusin
  • Methoxsalen
  • Trioxsalen