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大鼠和豚鼠灌注肺与肝脏对δ1-四氢大麻酚代谢的比较。

A comparison between the metabolism of delta 1-tetrahydrocannabinol by perfused lung and liver of rat and guinea-pig.

作者信息

Halldin M M, Isaac H, Widman M, Nilsson E, Ryrfeldt A

出版信息

Xenobiotica. 1984 Mar;14(3):277-82. doi: 10.3109/00498258409151412.

Abstract

The metabolism of delta 1-tetrahydrocannabinol (delta 1-THC) by lung and liver of rat and guinea-pig have been studied by isolated perfused-organ techniques. Metabolites were identified by t.l.c. and mass fragmentography. Biotransformation in lungs showed a different quantitative pattern to the livers in both species. 4"-Hydroxy-delta 1-THC was a major metabolite in both rat and guinea-pig lung. 7-Hydroxy-delta 1-THC was another major metabolite in guinea-pig lung, but a minor one in rat lung. 6 alpha-Hydroxy-delta 1-THC and 6,7-dihydroxy-delta 1-THC were formed in small quantities in both species. Small amounts of 6 beta-hydroxy-delta 1-THC were detected in guinea-pig lung in addition to the metabolites mentioned. Livers of rat and guinea-pig formed 7-hydroxy-delta 1-THC as the most abundant metabolite together with minor amounts of 6 alpha-hydroxy- and 6,7-dihydroxy-delta 1-THC. 6 beta-Hydroxy-delta 1-THC was a minor liver metabolite in guinea-pig, and was found in rat only in trace amounts, together with delta 1-THC-6-one. No side-chain hydroxylated metabolites were detected in rat liver, while guinea-pig liver formed trace amounts of 3"-hydroxy- and 4"-hydroxy-delta 1-THC.

摘要

采用离体灌注器官技术研究了大鼠和豚鼠肺与肝对δ1-四氢大麻酚(δ1-THC)的代谢。通过薄层层析和质量碎片谱法鉴定代谢产物。在这两个物种中,肺中的生物转化在定量模式上与肝脏不同。4″-羟基-δ1-THC是大鼠和豚鼠肺中的主要代谢产物。7-羟基-δ1-THC是豚鼠肺中的另一种主要代谢产物,但在大鼠肺中是次要代谢产物。6α-羟基-δ1-THC和6,7-二羟基-δ1-THC在这两个物种中生成量较少。除上述代谢产物外,在豚鼠肺中还检测到少量的6β-羟基-δ1-THC。大鼠和豚鼠的肝脏将7-羟基-δ1-THC作为最丰富的代谢产物生成,同时还有少量的6α-羟基-和6,7-二羟基-δ1-THC。6β-羟基-δ1-THC是豚鼠肝脏中的次要代谢产物,在大鼠中仅痕量存在,同时还有δ1-THC-6-酮。在大鼠肝脏中未检测到侧链羟基化代谢产物,而豚鼠肝脏生成痕量的3″-羟基-和4″-羟基-δ1-THC。

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