Metabolism of norcocaine, N-hydroxy norcocaine and cocaine-N-oxide in the rat.
Metabolism of norcocaine, N-hydroxy norcocaine and cocaine-N-oxide in the rat.
复制标题
大鼠体内去甲可卡因、N-羟基去甲可卡因和可卡因-N-氧化物的代谢。
DOI：
10.3109/00498257909038720
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发表时间：
1979
期刊：
影响因子：
--
通讯作者：
N. L. Vadlamani
中科院分区：
文献类型：
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作者：
A. Misra;R. Pontani;N. L. Vadlamani
1. 研究了大鼠静脉注射[3H]去甲可卡因、n -羟基[3H]去甲可卡因和可卡因- n -氧化物的代谢。2. 给药剂量为2 mg/kg的诺古柯碱在大鼠血浆、肝脏和脑中的生物t1 /2分别为0.4、1.6、0.5 h，注射后6 h中枢神经系统中未检出该化合物。96 h内尿、粪排出的诺古柯碱百分比分别为0.7和1.0。苯甲酰去甲烟碱、去甲烟碱、去甲烟碱甲酯和一种不明化合物随尿排出。3. n -羟去甲可卡因（5 mg/kg）在脑和血浆中的生物t1 /2分别为0.3和1.6 h， 96 h内仅1.3%和1.6%的剂量随尿液和粪便排出，n -羟苯甲酰去甲碱和n -羟去甲碱甲酯是主要的尿代谢产物。n -羟基去甲可卡因在体外不被肝微粒体代谢为去甲可卡因。大于7.5 mg/kg静脉注射剂量可导致大鼠因心肺骤停死亡。4. 可卡因n -氧化物（50 mg/kg静脉注射）的主要代谢产物是卵黄素n -氧化物甲酯；其他少量代谢物有可卡因（0.5%）、去甲可卡因（1%）、苯甲酰卵黄碱、卵黄碱、卵黄碱- n -氧化物，以及少量未代谢的化合物。可卡因n -氧化物致死率（100 mg/kg静脉注射）可能是由于对去甲可卡因和可卡因的代谢所致。
1. The metabolism of [3H]norcocaine, N-hydroxy[3H]norcocaine and cocaine-N-oxide has been investigated in rats after i.v. injection. 2. The biological t 1/2 of norcocaine (dose 2 mg/kg i.v.) in plasma, liver and brain were 0.4, 1.6, 0.5 h, respectively and the compound was not detectable in the central nervous system 6 h after injection. The % dose of norcocaine excreted unchanged in urine and faeces in 96 h were 0.7 and 1.0, respectively. Benzoylnorecgonine, norecgonine, norecgonine methyl ester and an unidentified compound were excreted in urine. 3. The biological t 1/2 of N-hydroxynorcocaine (5 mg/kg i.v.) in brain and plasma were 0.3, 1.6 h respectively and only 1.3 and 1.6% of dose were excreted unchanged in urine and faeces in 96 h. N-Hydroxybenzoylnorecgonine and N-hydroxynorecgonine methyl ester were the major urinary metabolites. N-hydroxynorcocaine was not metabolized to norcocaine in vitro by liver microsomes. Doses of greater than 7.5 mg/kg i.v. resulted in death of rats by cardiorespiratory arrest. 4. Cocaine-N-oxide (50 mg/kg i.v.) yielded ecgonine-N-oxide methyl ester as its major metabolite; other minor metabolites were cocaine (0.5%), norcocaine (1%), benzoylecgonine, ecgonine, ecgonine-N-oxide, along with minor amounts of unmetabolized compound. Lethality of cocaine-N-oxide (100 mg/kg i.v.) was possibly due to metabolism to norcocaine and cocaine.