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首页> 外文期刊>Acta Veterinaria Brno >Effect of Acute and Repeated Administration of Metttamphetamine on the Activity of CYP2D in Isolated Perfused Rat Liver
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Effect of Acute and Repeated Administration of Metttamphetamine on the Activity of CYP2D in Isolated Perfused Rat Liver

机译：反复反复服用甲氧苯丙胺对离体大鼠肝脏肝脏CYP2D活性的影响

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摘要

The aim of this study was to ascertain the influence of acute and repeated methamphetamine administration on metabolic activity of CYP2D2. The study was performed in the model of isolated perfused rat liver using dextromethorphan as a specific markerof CYP2D2 activity. Acute administration of methamphetamine (10,20 or 40 mg/kg, i.p., once daily for two days) significantly increased dextrorphan O-forrnation in the isolated liver mediated by CYP2D2 at all investigated doses in the 120th min of liver perfusion. Repeated administration of methamphetamine (10,20 or 40 mg/kg, i.p., once daily for six days) significantly stimulated dextromethorphan O-demethylation via CYP2D2 dose-dependently. Thus, an induction of CYP2D2 metabolic activity was proved in these experiments. With regard to a high level of homology between human and rat CYP isoform studied, the results may have clinical impact in pharmacotherapy of methamphetamine abusers.
机译：这项研究的目的是确定急性和反复服用甲基苯丙胺对CYP2D2代谢活性的影响。该研究是在分离的大鼠肝脏灌流模型中使用右美沙芬作为CYP2D2活性的特异性标志物进行的。在肝灌注的第120分钟内，在所有研究剂量下，急性给予甲基苯丙胺（10,20或40 mg / kg，腹膜内，每天一次，连续两天）显着增加了由CYP2D2介导的分离的肝脏中右啡烷O穿孔。重复服用甲基苯丙胺（10,20或40 mg / kg，腹腔注射，每天一次，连续六天）可通过CYP2D2剂量依赖性显着刺激右美沙芬O-去甲基化。因此，在这些实验中证明了CYP2D2代谢活性的诱导。关于研究的人类和大鼠CYP同工型之间的高度同源性，该结果可能对甲基苯丙胺滥用者的药物治疗产生临床影响。

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