合成卡西酮继续在全球秘密药物市场上扩散。N-乙基降戊酮(也称为N-乙基戊酮或乙苯酮)是一种流行的新兴卡西酮,然而,关于其毒理学和药理学的信息很少。在这里,我们描述了分析量化,临床表现,N-乙基降戊酮的药理作用机制。使用与串联质谱联用的液相色谱(LC-MS/MS)来定量从人类病例获得的血液中的N-乙基降戊酮。描述了中毒个体表现出的临床特征。N-乙基降戊酮对多巴胺(DAT)的质膜转运蛋白的活性,使用体外测定法评估去甲肾上腺素(NET)和5-HT(SERT),该测定法测量了大鼠脑突触体中[3H]神经递质的摄取抑制和诱发释放。我们的LC-MS/MS方法测定了N-乙基降戊酮的浓度,检出限为1和5ng/mL,分别。定量从5到500ng/mL呈线性,方法具有特异性和重现性。在临床病例中,N-乙基降戊酮的循环浓度范围为7至170ng/mL,相关症状包括心悸,心动过速,激动,幻觉,昏迷和死亡。N-乙基降戊酮在DAT时是有效的抑制剂(IC50=37nM),NET(IC50=105nM)和SERT(IC50=383nM),但不显示转运蛋白释放活性。我们提出了一种在人类案例中定量N-乙基降戊酮的有效方法。该药物是一种精神运动兴奋剂,能够引起严重的心血管和神经系统副作用,可能是致命的。体外研究结果表明,N-乙基降戊酮通过有效阻断DAT和NET发挥其作用,从而提高大脑和外周的多巴胺和去甲肾上腺素的细胞外水平。
Synthetic cathinones continue to proliferate in clandestine drug markets worldwide. N-ethylnorpentylone (also known as N-ethylpentylone or ephylone) is a popular emergent cathinone, yet little information is available about its toxicology and pharmacology. Here we characterize the analytical quantification, clinical presentation, and pharmacological mechanism of action for N-ethylnorpentylone. Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) was used to quantify N-ethylnorpentylone in blood obtained from human cases. Clinical features exhibited by the intoxicated individuals are described. The activity of N-ethylnorpentylone at plasma membrane transporters for dopamine (DAT), norepinephrine (NET) and 5-HT (SERT) was assessed using in vitro assays measuring uptake inhibition and evoked release of [3 H] neurotransmitters in rat brain synaptosomes. Our LC-MS/MS method assayed N-ethylnorpentylone concentrations with limits of detection and quantification of 1 and 5 ng/mL, respectively. Quantitation was linear from 5 to 500 ng/mL, and the method displayed specificity and reproducibility. Circulating concentrations of N-ethylnorpentylone ranged from 7 to 170 ng/mL in clinical cases, and the associated symptoms included palpitations, tachycardia, agitation, hallucinations, coma and death. N-Ethylnorpentylone was a potent inhibitor at DAT (IC50 = 37 nM), NET (IC50 = 105 nM) and SERT (IC50 = 383 nM) but displayed no transporter releasing activity. We present a validated method for quantifying N-ethylnorpentylone in human
case work. The drug is a psychomotor stimulant capable of inducing serious cardiovascular and neurological side-effects which can be fatal. In vitro findings indicate that N-ethylnorpentylone exerts its effects by potent blockade of DAT and NET, thereby elevating extracellular levels of dopamine and norepinephrine in the brain and periphery.