In vitro effect of additives in benzodiazepine solutions on the superoxide anion-generating system in polymorphonuclear leucocytes

Hiroshi Morisaki, T. Tanaka, Y. Ishimura, J. Takeda, H. Sekiguchi, M. Nagano

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6 Citations (Scopus)


Inhibitory effects of diazepam and flunitrazepam on the superoxide anion (O2-) -generating system in granulocytes were examined for their clinical relevance. When the effects of commercial solutions and pure preparations were compared using porcine and human polymorphonuclear leucocytes in vitro, the solutions were found to be more inhibitory than the pure drugs by 4-11 times, indicating that inhibition was caused mainly by the additives in the solutions. Concentrations of the additives required for 50% maximal inhibition of the system were 2.3, 7.5 and 0.9 μl ml-1 for propylene glycol, ethanol and benzyl alcohol, respectively, while those of pure diazepam and flunitrazepam were 220 and 190 μg ml-1, respectively, under comparable conditions. However, plasma concentrations of the benzodiazepines and their additives during clinical use were far less than these inhibitory concentrations, indicating that they had no appreciable effect on the O2--generating system in polymorphonuclear leucocytes of patients.

Original languageEnglish
Pages (from-to)97-102
Number of pages6
JournalBritish Journal of Anaesthesia
Issue number1
Publication statusPublished - 1991 Jan



  • Blood: neutrophils
  • Hypnotics: benzodiazepines
  • Pharmacology: additives, preservatives

ASJC Scopus subject areas

  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Mathematics(all)
  • Statistics and Probability
  • Agricultural and Biological Sciences (miscellaneous)
  • Anesthesiology and Pain Medicine

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