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 language | English |
|---|---|
| Pages (from-to) | 1675-1678 |
| Number of pages | 4 |
| Journal | Biochemical Pharmacology |
| Volume | 35 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - May 15 1986 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Pharmacology
Cite this
Effects of glutathione and phenobarbital on the toxicity of codeinone. / Nagamatsu, Kunisuke; Inoue, Kazuhide; Terao, Tadao; Toki, Satoshi.
In: Biochemical Pharmacology, Vol. 35, No. 10, 15.05.1986, p. 1675-1678.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Effects of glutathione and phenobarbital on the toxicity of codeinone
AU - Nagamatsu, Kunisuke
AU - Inoue, Kazuhide
AU - Terao, Tadao
AU - Toki, Satoshi
PY - 1986/5/15
Y1 - 1986/5/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0022458157&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0022458157&partnerID=8YFLogxK
U2 - 10.1016/0006-2952(86)90322-9
DO - 10.1016/0006-2952(86)90322-9
M3 - Article
C2 - 3707597
AN - SCOPUS:0022458157
VL - 35
SP - 1675
EP - 1678
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
SN - 0006-2952
IS - 10
ER -