苯环利定（PCP）与δ9-四氢大麻酚（THC）在大鼠体内的代谢相互作用。

Metabolic interactions of phencyclidine (PCP) and delta 9-tetrahydrocannabinol (THC) in the rat.

作者信息

Lamé M W, Husain S

出版信息

Pharmacol Biochem Behav. 1986 Oct;25(4):827-33. doi: 10.1016/0091-3057(86)90394-1.

Abstract

The in vitro effects of THC on the metabolism of PCP by rat liver were determined. Samples containing 1 mM PCP were incubated for 1 hr at 37 degrees C with an NADPH-generating system containing 10,000 X g supernatant or Ca++-precipitated rat liver microsomes. These incubations were carried out in the presence or absence of THC and at the end of 1 hr, PCP metabolites were determined by gas chromatography. In the presence of 0.1, 0.05, 0.025 and 0.0125 mM THC, the production of 1-(1-phenyl-4-hydroxycyclohexyl)piperidine (metabolite I) by the 10,000 X g supernatant was decreased by 46, 29, 23 and 16% respectively. Similarly, production of 1-(1-phenylcyclohexyl)-4-hydroxypiperidine (metabolite II) was reduced significantly by 58, 44, 34 and 23% with the respective concentrations of THC. However, the production of 1-phenylcyclohexylamine (metabolite III) was increased by 18, 32, 30 and 22% with 0.1, 0.05, 0.025 and 0.0125 mM THC. Incubations with Ca++-precipitated liver microsomes revealed similar trends in PCP metabolism in the presence or absence of THC. Metabolites I and II were reduced by 62 and 67% by 0.1 mM THC. Another concentration of THC (0.025 mM) caused a 50 and 62% decrease in I and II. These observations suggest that THC alters the in vitro microsomal metabolism of PCP.

摘要

测定了四氢大麻酚（THC）对大鼠肝脏中苯环己哌啶（PCP）代谢的体外作用。将含有1 mM PCP的样品与含有10,000×g上清液或Ca++沉淀的大鼠肝脏微粒体的NADPH生成系统在37℃下孵育1小时。这些孵育在有或没有THC的情况下进行，1小时结束时，通过气相色谱法测定PCP代谢物。在存在0.1、0.05、0.025和0.0125 mM THC的情况下，10,000×g上清液产生1-(1-苯基-4-羟基环己基)哌啶（代谢物I）的量分别减少了46%、29%、23%和16%。同样，在相应浓度的THC作用下，1-(1-苯基环己基)-4-羟基哌啶（代谢物II）的产生量显著减少了58%、44%、34%和23%。然而，在0.1、0.05、0.025和0.0125 mM THC作用下，1-苯基环己胺（代谢物III）的产生量增加了18%、32%、30%和22%。用Ca++沉淀的肝脏微粒体进行孵育，发现在有或没有THC的情况下，PCP代谢呈现相似趋势。0.1 mM THC使代谢物I和II分别减少了62%和67%。另一种浓度的THC（0.025 mM）使代谢物I和II分别减少了50%和62%。这些观察结果表明，THC改变了PCP的体外微粒体代谢。