Effects of glutathione and phenobarbital on the toxicity of codeinone.
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-3-H]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.
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Nagamatsu
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Inoue
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T
Terao
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Toki
D000818:Animals; D003061:Codeine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity; D005978:Glutathione / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009270:Naloxone / Q000494:pharmacology; D010634:Phenobarbital / Q000494:pharmacology*; D012640:Seizures / Q000139:chemically induced; D014316:Tritium
D014316:Tritium; C046414:6-codeinone; D009270:Naloxone; D005978:Glutathione; D003061:Codeine; D010634:Phenobarbital