Effects of chlordiazepoxide and diazepam on respiration and oxidative phosphorylation in rat brain mitochondria

Leon F. Davis, Edward E. Gatz, John R. Jones

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

The effects of chlordiazepoxide and diazepam on respiration and oxidative phosphorylation of succinate, pyruvate and alpha-ketoglutarate by rat brain mitochondria were investigated polarographically. Chlordiazepoxide and diazepam were each found to decrease respiration as evidenced from decreased state 3 and 2,4-dinitrophenol-stimulated state 4 oxygen uptake in the presence of the above three substrates. The decreases in state 3 and 2,4-dinitrophenol-stimulated state 4 rates were related to the added concentration of each drug. With respiratory control indices and ADP:O ratios as an index of oxidative phosphorylation, it was found that chlordiazepoxide and diazepam decreased oxidative phosphorylation. The decrease in oxidative phosphorylation may be due in part to an increase in adenosine triphosphatase activity as evidenced from the increased rates of oxygen uptake during state 4. To achieve a given effect on the above mitochondrial functions, it was found that the concentration in vitro of chlordiazepoxide had to be five to seven times greater than that of diazepam.

Original languageEnglish (US)
Pages (from-to)1883-1887
Number of pages5
JournalBiochemical Pharmacology
Volume20
Issue number8
DOIs
StatePublished - Aug 1971

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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