title: Psoralen pharmacology: studies on metabolism and enzyme induction.
abstract: Psoralens, tricyclic furocoumarins with potent photosensitizing properties in the skin, are now widely used in the treatment of several dermatologic diseases. In this study, the metabolism of 4,5',8-trimethylpsoralen (TMP) and 8-methoxypsoralen (8-MOP) was studied in mouse liver. Orally administered TMP is transformed into several metabolites, the major one of which is 4,8-dimethyl-5'-carboxypsoralen (DMCP) in both humans and mice. Orally administered 8-MOP is metabolized into at least 5 fluorescent moieties, including 8-hydroxypsoralen, the 4'5'-dihydro-diol of 8-MOP, and furocoumaric acid. The effects of 3 psoralens, 8-MOP, TMP, and isopsoralen (angelicin) on hepatic microsomal drug-metabolizing enzymes and cytochrome P-450 were assessed in mice and rats. Administered orally to CD-1 mice daily for 6 days, 8-MOP caused twofold to threefold increases in hepatic aryl hydrocarbon hydroxylase (AHH), ethylmorphine N-demethylase, and cytochrome P-450. The absorbance maximum of the induced cytochrome was at 450 nm. Aniline hydroxylase activity was unchanged. Chronic administration of 8-MOP to Skh:hairless-1 mice caused significant enhancement of hepatic ethylmorphine N-demethylase and cytochrome P-450 but had no effect on AHH, whereas chronically administered TMP had no significant effect on any of these parameters.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects; D011564:Furocoumarins / Q000378:metabolism / Q000494:pharmacology*; D006168:Guinea Pigs; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D011564:Furocoumarins; D001189:Aryl Hydrocarbon Hydroxylases