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Differential inhibition of human liver phenacetin O-deethylation by histamine and four histamine H2-receptor antagonists.
Xenobiotica. 1988 Apr; 18(4):381-7.X

Abstract

1. The effects of histamine and four histamine H-2 receptor antagonists on phenacetin O-deethylation by microsomal preparations of four human livers was quantified by a radiometric-thin layer chromatographic method. 2. Histamine and three of these drugs, namely cimetidine, ranitidine and famotidine, were weak inhibitors of this cytochrome P-450-catalysed O-deethylation, but mifentidine was a potent competitive inhibitor with a Ki in the range 40-70 microM. 3. Cimetidine, histamine and mifentidine are all 4(5)-substituted imidazole derivatives, and the contrast between the very weak inhibitory effects of cimetidine and histamine, and the more potent effect of mifentidine, suggests that the imidazole moiety may play little role in the inhibition of phenacetin O-deethylase by mifentidine. 4. The demonstration that cimetidine, ranitidine and histamine were all poor inhibitors of phenacetin oxidation further suggests the possible lack of identity between the human liver cytochrome P-450 isoenzymes responsible for catalyzing the oxidation of metoprolol and phenacetin. This follows from recognizing that metoprolol oxidation is known, from both in vivo and in vitro studies, to be strongly inhibited by both of these H-2 receptor antagonists and from in vitro studies also to be inhibited by histamine.

Authors+Show Affiliations

Reilly PE
Department of Biochemistry, University of Queensland, St. Lucia, Australia.
Mason SR
No affiliation info available
Gillam EM
No affiliation info available

MeSH

Binding SitesBinding, CompetitiveCatalysisChromatography, Thin LayerCimetidineCytochrome P-450 CYP1A2FamotidineHistamineHistamine H2 AntagonistsHumansImidazolesMicrosomes, LiverOxidation-ReductionOxidoreductasesRanitidineThiazoles

Pub Type(s)

Journal Article

Language

eng

PubMed ID

2899931

Citation

Reilly, P E., et al. "Differential Inhibition of Human Liver Phenacetin O-deethylation By Histamine and Four Histamine H2-receptor Antagonists." Xenobiotica; the Fate of Foreign Compounds in Biological Systems, vol. 18, no. 4, 1988, pp. 381-7.
Reilly PE, Mason SR, Gillam EM. Differential inhibition of human liver phenacetin O-deethylation by histamine and four histamine H2-receptor antagonists. Xenobiotica. 1988;18(4):381-7.
Reilly, P. E., Mason, S. R., & Gillam, E. M. (1988). Differential inhibition of human liver phenacetin O-deethylation by histamine and four histamine H2-receptor antagonists. Xenobiotica; the Fate of Foreign Compounds in Biological Systems, 18(4), 381-7.
Reilly PE, Mason SR, Gillam EM. Differential Inhibition of Human Liver Phenacetin O-deethylation By Histamine and Four Histamine H2-receptor Antagonists. Xenobiotica. 1988;18(4):381-7. PubMed PMID: 2899931.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential inhibition of human liver phenacetin O-deethylation by histamine and four histamine H2-receptor antagonists. AU - Reilly,P E, AU - Mason,S R, AU - Gillam,E M, PY - 1988/4/1/pubmed PY - 1988/4/1/medline PY - 1988/4/1/entrez SP - 381 EP - 7 JF - Xenobiotica; the fate of foreign compounds in biological systems JO - Xenobiotica VL - 18 IS - 4 N2 - 1. The effects of histamine and four histamine H-2 receptor antagonists on phenacetin O-deethylation by microsomal preparations of four human livers was quantified by a radiometric-thin layer chromatographic method. 2. Histamine and three of these drugs, namely cimetidine, ranitidine and famotidine, were weak inhibitors of this cytochrome P-450-catalysed O-deethylation, but mifentidine was a potent competitive inhibitor with a Ki in the range 40-70 microM. 3. Cimetidine, histamine and mifentidine are all 4(5)-substituted imidazole derivatives, and the contrast between the very weak inhibitory effects of cimetidine and histamine, and the more potent effect of mifentidine, suggests that the imidazole moiety may play little role in the inhibition of phenacetin O-deethylase by mifentidine. 4. The demonstration that cimetidine, ranitidine and histamine were all poor inhibitors of phenacetin oxidation further suggests the possible lack of identity between the human liver cytochrome P-450 isoenzymes responsible for catalyzing the oxidation of metoprolol and phenacetin. This follows from recognizing that metoprolol oxidation is known, from both in vivo and in vitro studies, to be strongly inhibited by both of these H-2 receptor antagonists and from in vitro studies also to be inhibited by histamine. SN - 0049-8254 UR - https://www.unboundmedicine.com/medline/citation/2899931/Differential_inhibition_of_human_liver_phenacetin_O_deethylation_by_histamine_and_four_histamine_H2_receptor_antagonists_ DB - PRIME DP - Unbound Medicine ER -