Nizatidine, a new histamine H2-receptor antagonist, and hepatic oxidative drug metabolism in the rat: A comparison with structurally related compounds

C. G. Meredith, K. V. Speeg, S. Schenker

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


The effects of nizatidine (a new H2-receptor antagonist) and of related compounds were studies on oxidative drug metabolism in the rat both in vivo and in vitro. Nizatidine is a structural analog of the H2-receptor antagonists ICI 125,211 (Tiotidine) and ranitidine (Zantac). Nizatidine (120 mg/kg, ip) had no effect on the [14C]aminopyrine (ABT) or [14C]caffeine breath (CBT) tests, nor on the clearance from plasma of aminopyrine despite high tissue and plasma concentrations of nizatidine. Binding of nizatidine (1 mm) to rat hepatic microsomal P-450 determined by spectral analysis was not observed. In vitro aminopyrine demethylation was inhibited by nizatidine only at high concentrations (Ki = 92 mm). Cimetidine, ICI 125,211, and imidazole bind avidly to rat hepatic microsomal cytochrome P-450 and are potent inhibitors of aminopyrine demethylation in vitro. Imidazole inhibited the aminopyrine breath test, while imidazole, ranitidine, and ICI 125,211 inhibited the caffeine breath in vivo. These data indicate that nizatidine has no acute inhibitory effect on hepatic oxidative drug metabolism in the rat, both in vitro and in vivo. The composite structural-activity data suggest that inhibition of in vivo oxidative drug metabolism by H2-antagonists may not depend primarily on either the imidazole ring side chain or the thiazole ring per se. Furthermore, the in vivo inhibition may not correlate with in vitro data.

Original languageEnglish (US)
Pages (from-to)315-324
Number of pages10
JournalToxicology and Applied Pharmacology
Issue number2
StatePublished - Feb 1985

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology


Dive into the research topics of 'Nizatidine, a new histamine H<sub>2</sub>-receptor antagonist, and hepatic oxidative drug metabolism in the rat: A comparison with structurally related compounds'. Together they form a unique fingerprint.

Cite this