Studies on the beta-oxidative metabolism of delta 1- and delta 6-tetrahydrocannabinol in the mouse. The in vivo biotransformation of metabolites oxidized in the side chain.
Studies on the beta-oxidative metabolism of delta 1- and delta 6-tetrahydrocannabinol in the mouse. The in vivo biotransformation of metabolites oxidized in the side chain.
复制标题
小鼠体内 Delta 1- 和 Delta 6-四氢大麻酚的 β 氧化代谢研究。
DOI：
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发表时间：
1985
影响因子：
3.9
通讯作者：
J. Leuschner
中科院分区：
文献类型：
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作者：
D. Harvey;J. Leuschner
5”-羟基-δ 1-四氢大麻酚（THC）、5”-羟基-[5”，5”-2H2] δ 1-THC、δ 1-THC-5”-酸和δ 6-THC-5”-酸的代谢在小鼠腹腔内给予化合物后，通过气相色谱和质谱联用检查。所有三种δ 1-THC衍生物的代谢特征相似，并显示出通过β-氧化途径的广泛代谢。鉴定了9种代谢产物，其中7种含有C3侧链。δ 1-THC衍生物的主要代谢产物是7-羟基-4”，5”-双，去甲-δ 1-THC-3”-酸。在δ 6-THC-5”-酸中发现了类似的代谢物。没有发现侧链中具有偶数碳原子的代谢物，尽管据报道这些代谢物是由THC和几个物种中的几种其他大麻素在体内产生的。因此，在C-5”处初始羟基化后，β-氧化途径似乎直接导致在链中含有奇数个碳原子的侧链降解的大麻素代谢物的形成，但最初不导致含有偶数个碳原子的那些代谢物的形成。这些被认为是通过最初的α-氧化形成的，以得到C4侧链，然后C4侧链可以经历β-氧化成具有C2侧链的大麻素。在这些实验中观察到的广泛的β-氧化，加上在小鼠中缺乏来自δ 1-THC本身的相应大麻素，表明5”-羟基化是这些化合物形成的速率决定步骤。
The metabolism of 5"-hydroxy-delta 1-tetrahydrocannabinol (THC), 5"-hydroxy-[5",5"-2H2]delta 1-THC, delta 1-THC-5"-oic acid, and delta 6-THC-5"-oic acid was examined by combined gas chromatography and mass spectrometry in the mouse after intraperitoneal administration of the compounds. Metabolic profiles from all three derivatives of delta 1-THC were similar and showed extensive metabolism by the beta-oxidation pathway. Nine metabolites were identified, seven of which contained a C3 side chain. The major metabolite from the delta 1-THC derivatives was 7-hydroxy-4",5"-bis,nor-delta 1-THC-3"-oic acid. Similar metabolites were found with delta 6-THC-5"-oic acid. No metabolites were found with even numbers of carbon atoms in the side chain although these have been reported to be produced in vivo by THC and several other cannabinoids in several species. Thus, the beta-oxidation route, after initial hydroxylation at C-5", appears to be directly responsible for formation of side chain-degraded cannabinoid metabolites containing odd numbers of carbon atoms in the chain but not initially for those metabolites containing an even number of carbon atoms. These are presumed to be formed by initial alpha-oxidation to give a C4 side chain which can then undergo beta-oxidation to the cannabinoids with C2 side chains. The extensive beta-oxidation observed in these experiments, coupled with the absence of corresponding cannabinoids from delta 1-THC itself in the mouse, suggests that 5"-hydroxylation is the rate-determining step in the formation of these compounds.