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Interactions of phenethylamine‐derived psychoactive substances of the 2C‐series with human monoamine oxidases
Drug Testing and Analysis ( IF 2.6 ) Pub Date : 2018-09-28 , DOI: 10.1002/dta.2494
Lea Wagmann 1 , Simon D. Brandt 2 , Alexander Stratford 3 , Hans H. Maurer 1 , Markus R. Meyer 1
Affiliation  

Psychoactive substances of the 2C‐series (2Cs) are phenethylamine‐derived designer drugs that can induce psychostimulant and hallucinogenic effects. Chemically, the classic 2Cs contain two methoxy groups in positions 2 and 5 of the phenyl ring, whereas substances of the so‐called FLY series contain rigidified methoxy groups integrated in a 2,3,6,7‐tetrahydrobenzo[1,2‐b:4,5‐b’]difuran core. One of the pharmacological features that has not been investigated in detail is the inhibition of monoamine oxidase (MAO). Inhibition of this enzyme can cause elevated monoamine levels that have been associated with adverse events such as agitation, nausea, vomiting, tachycardia, hypertension, or seizures. The aim of this study was to extend the knowledge surrounding the potential of MAO inhibition for 17 test drugs, which consisted of 12 2Cs (2C‐B, 2C‐D, 2C‐E, 2C‐H, 2C‐I, 2C‐N, 2C‐P, 2C‐T‐2, 2C‐T‐7, 2C‐T‐21, bk‐2C‐B, and bk‐2C‐I) and five FLY analogs (2C‐B‐FLY, 2C‐E‐FLY, 2C‐EF‐FLY, 2C‐I‐FLY, and 2C‐T‐7‐FLY). The extent of MAO inhibition was assessed using an established in vitro procedure based on heterologously expressed enzymes and analysis by hydrophilic interaction liquid chromatography–high resolution tandem mass spectrometry. Thirteen test drugs showed inhibition potential for MAO‐A and 11 showed inhibition of MAO‐B. In cases where MAO‐A IC50 values were determined, values ranged from 10 to 125 μM (7 drugs) and from 1.7 to 180 μM for MAO‐B (9 drugs). In the absence of detailed clinical information on most test drugs, it is concluded that a pharmacological contribution of MAO inhibition cannot be excluded and that further studies are warranted.

中文翻译:

2C系列苯乙胺衍生的精神活性物质与人单胺氧化酶的相互作用

2C系列(2Cs)的精神活性物质是苯乙胺衍生的设计药物,可引起精神刺激和致幻作用。化学上,经典的2C在苯环的2和5位上含有两个甲氧基,而所谓的FLY系列物质则包含整合在2,3,6,7-四氢苯并[1,2-b]中的刚性甲氧基:4,5‐b']呋喃核。尚未详细研究的药理学特征之一是单胺氧化酶(MAO)的抑制作用。抑制该酶可导致单胺水平升高,而单胺水平升高则与不良事件(如躁动,恶心,呕吐,心动过速,高血压或癫痫发作)有关。这项研究的目的是扩展对17种受试药物MAO抑制潜力的认识,其中包括12种2C(2C-B,2C-D,2C-E,2C‐H,2C‐I,2C‐N,2C‐P,2C‐T‐2、2C‐T‐7、2C‐T‐21,bk‐2C‐B和bk‐2C‐I)和五个FLY类似物(2C‐B‐FLY,2C‐E‐FLY,2C‐EF‐FLY,2C‐I‐FLY和2C‐T‐7‐FLY)。使用建立在异源表达酶基础上的体外方法并通过亲水相互作用液相色谱-高分辨率串联质谱分析对MAO的抑制程度进行评估。十三种受试药物对MAO-A表现出抑制作用,而11种对MAO-B表现出抑制作用。在MAO‐A IC的情况下 使用建立在异源表达酶基础上的体外方法并通过亲水相互作用液相色谱-高分辨率串联质谱分析对MAO的抑制程度进行评估。十三种受试药物对MAO-A表现出抑制作用,而11种对MAO-B表现出抑制作用。在MAO‐A IC的情况下 使用建立在异源表达酶基础上的体外方法并通过亲水相互作用液相色谱-高分辨率串联质谱分析对MAO的抑制程度进行评估。十三种受试药物对MAO-A表现出抑制作用,而11种对MAO-B表现出抑制作用。在MAO‐A IC的情况下确定了50个值,对于MAO-B(9种药物),值范围从10到125μM(从7种药物)到1.7至180μM。在缺乏大多数测试药物的详细临床信息的情况下,得出的结论是不能排除MAO抑制作用的药理作用,因此有必要进行进一步的研究。
更新日期:2018-09-28
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