Interactions of the histamine H2-receptor antagonist etintidine with rat liver cytochrome P-450: a comparison with cimetidine

Naunyn Schmiedebergs Arch Pharmacol. 1987 Oct;336(4):453-8. doi: 10.1007/BF00164882.


The two imidazole histamine H2-receptor antagonists etintidine and cimetidine interact with the rat liver microsomal cytochrome P-450. From type II spectral changes follows that the affinity of rat liver microsomal preparations for etintidine is about 5 times as high as for cimetidine when comparing both high and low affinity binding sites. After pretreatment with phenobarbital etintidine inhibited benzphetamine N-demethylation competitively (app. Ki: 4.0 mmol/l). Cimetidine inhibited benzphetamine N-demethylation in the same range. After pretreatment with phenobarbital both drugs inhibited the oxidation of benzo(a)pyrene for which etintidine showed a higher inhibitory potency than cimetidine. However, this oxidation could not be inhibited when microsomes of 5,6-benzoflavone pretreated rats were used. After pretreatment with 5,6-benzoflavone only etintidine but not cimetidine inhibited the O-deethylation of ethoxyresorufin competitively (app. Ki: 0.2 mmol/l). Etintidine and cimetidine were metabolized by rat liver microsomes to their corresponding sulphoxides. In conclusion, etintidine may cause mainly the same drug interactions as cimetidine but seems to be a more potent inhibitor.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Cimetidine / metabolism
  • Cimetidine / pharmacology*
  • Cytochrome P-450 Enzyme System / metabolism*
  • Histamine H2 Antagonists / metabolism
  • Histamine H2 Antagonists / pharmacology*
  • Imidazoles / metabolism
  • Imidazoles / pharmacology*
  • In Vitro Techniques
  • Liver / drug effects
  • Liver / enzymology*
  • Male
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / enzymology
  • Oxidation-Reduction
  • Rats
  • Rats, Inbred Strains


  • Histamine H2 Antagonists
  • Imidazoles
  • Cimetidine
  • Cytochrome P-450 Enzyme System
  • etintidine