Effects of glutathione and phenobarbital on the toxicity of codeinone

Kunisuke Nagamatsu, Kazuhide Inoue, Tadao Terao, Satoshi Toki

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

The ability of sulfhydryl compounds to provide protection against the acute toxicity of codeinone, a toxic metabolite of codeine, was investigated in mice. Subcutaneous administration of codeinone produced a slight reduction in hepatic glutathione concentration. Pretreatment of the mice with glutathione or cysteine significantly increased the survival rate for mice given a lethal dose of codeinone (10 mg/kg). The lethality of codeine was lowered by naloxone, whereas that of codeinone was not blocked by naloxone. The strychnine-like convulsant action of codeinone could be prevented by phenobarbital pretreatment. Glutathione pretreatment reduced the amounts of radioactivity in tissues of mice injected with [N-methyl-3H]codeinone. A possible explanation for these observations is that glutathione reacts in vivo with codeinone and plays a role as a scavenger of this compound. This assumption is supported by the observation that codeinone reacts non-enzymatically with glutathione under physiological conditions.

Original languageEnglish
Pages (from-to)1675-1678
Number of pages4
JournalBiochemical Pharmacology
Volume35
Issue number10
DOIs
Publication statusPublished - May 15 1986
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Pharmacology

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