Diazepam-induced decrease in histamine turnover in mouse brain

Ryozo Oishi, Masahiro Nishibori, Yoshinori Itoh, Kiyomi Saeki

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Abstract

The effect of diazepam on brain histamine turnover was examined in mice. The steady state levels of histamine and tele-methylhistamine remained unchanged following the i.p. administration of 0.2-20 mg/kg of diazepam. However, diazepam in doses over 5 mg/kg significantly decreased histamine turnover, as estimated from the accumulation of tele-methylhistamine after pargyline treatment. Other benzodiazepines such as chlordiazepoxide, nitrazepam and estazolam in high doses also decreased histamine turnover. The inhibitory effect of diazepam on histamine turnover was antagonized by the pretreatment with a benzodiazepine antagonist Ro 15-1788. The histamine turnover was significantly inhibited by 2 mg/kg of muscimol. Diazepam (0.2-1 mg/kg) markedly and dose-dependently potentiated the inhibitory effect of 1 mg/kg of muscimol from non-significant to highly significant levels. The potentiation by diazepam was also antagonized by Ro 15-1788. Therefore, diazepam probably decreases histamine turnover in the brain via the benzodiazepine-GABA receptor complex.

Original languageEnglish
Pages (from-to)337-342
Number of pages6
JournalEuropean Journal of Pharmacology
Volume124
Issue number3
DOIs
Publication statusPublished - May 27 1986

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Keywords

  • Benzodiazepines
  • Diazepam
  • Histamine turnover
  • Muscimol
  • Ro 15-1788
  • tele-Methylhistamine

ASJC Scopus subject areas

  • Pharmacology

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