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Inhibition of mirtazapine metabolism by Ecstasy (MDMA) in isolated perfused rat liver model

机译:迷魂药(MDMA)在离体灌流大鼠肝脏模型中对米氮平的代谢抑制

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摘要

BackgroundNowadays MDMA (3,4-methylendioxymethamphetamine), known as ecstasy, is widely abused among the youth because of euphoria induction in acute exposure. However, abusers are predisposed to depression in chronic consumption of this illicit compound.Mirtazapine (MRZ), an antidepressant agent, may be prescribed in MDMA-induced depression. MRZ is extensively metabolized in liver by CYP450 isoenzymes. 8-hydroxymirtazapine (8-OH) is mainly produced by CYP2D6. N-desmethylmirtazapine (NDES) is generated by CYP3A4.MDMA is also metabolized by the mentioned isoenzymes and demonstrates mechanism-based inhibition (MBI) in association with CYP2D6. Several studies revealed that MDMA showed inhibitory effects on CYP3A4.In the present study, our aim was to evaluate the impact of MDMA on the metabolism of MRZ in liver.Therefore, isolated perfused rat liver model was applied as our model of choice in this assessment.
机译:背景技术如今,由于摇头丸引起急性暴露,因此被称为摇头丸的摇头丸(3,4-甲基二乙氧基甲基苯丙胺)在年轻人中被广泛滥用。但是,滥用者在长期服用这种非法化合物时易患上抑郁症。抗抑郁药米氮平(MRZ)可在MDMA引起的抑郁症中处方。 MRZ通过CYP450同工酶在肝脏中广泛代谢。 8-hydroxymirtazapine(8-OH)主要由CYP2D6产生。 N-desmethylmirtazapine(NDES)由CYP3A4产生,MDMA也被上述同工酶代谢,并显示与CYP2D6相关的基于机制的抑制作用(MBI)。多项研究显示MDMA对CYP3A4有抑制作用。在本研究中,我们的目的是评估MDMA对肝脏MRZ代谢的影响。因此,本研究选择了离体灌注大鼠肝脏模型作为我们的选择模型。

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