Wagmann Lea, Brandt Simon D, Stratford Alexander, Maurer Hans H, Meyer Markus R
Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Center for Molecular Signaling (PZMS), Saarland University, Homburg, Germany.
School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK.
Drug Test Anal. 2019 Feb;11(2):318-324. doi: 10.1002/dta.2494. Epub 2018 Sep 28.
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 IC 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.
2C系列精神活性物质（2Cs）是苯乙胺类设计药物，可产生精神兴奋和致幻作用。从化学结构上看，经典的2Cs在苯环的2位和5位含有两个甲氧基，而所谓的FLY系列物质则含有整合在2,3,6,7-四氢苯并[1,2-b:4,5-b']二呋喃核心中的刚性甲氧基。尚未详细研究的药理学特征之一是对单胺氧化酶（MAO）的抑制作用。抑制该酶可导致单胺水平升高，这与诸如躁动、恶心、呕吐、心动过速、高血压或癫痫发作等不良事件有关。本研究的目的是扩展关于17种受试药物MAO抑制潜力的知识，这些受试药物包括12种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和bk-2C-I）和5种FLY类似物（2C-B-FLY、2C-E-FLY、2C-EF-FLY、2C-I-FLY和2C-T-7-FLY）。使用基于异源表达酶的既定体外程序并通过亲水相互作用液相色谱-高分辨率串联质谱法分析来评估MAO抑制程度。13种受试药物显示出对MAO-A的抑制潜力，11种显示出对MAO-B的抑制作用。在测定MAO-A IC值的情况下，MAO-A的值范围为10至125μM（7种药物），MAO-B的值范围为1.7至180μM（9种药物）。由于大多数受试药物缺乏详细的临床信息，得出的结论是不能排除MAO抑制的药理学作用，有必要进行进一步研究。
