Citation

Wagmann L, Brandt SD, Stratford A, Maurer HH, Meyer MR. Drug Test. Anal. 2019; 11(2): 318-324.

Affiliation

Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Center for Molecular Signaling (PZMS), Saarland University, Homburg, Germany.

Copyright

(Copyright © 2019, John Wiley and Sons)

DOI

10.1002/dta.2494

PMID

30188017

Abstract

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 includes 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 twelve 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, 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 could be determined, values ranged from 10 to 125 μM (7 drugs) and 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.

This article is protected by copyright. All rights reserved.

Language: en

Keywords

HILIC-HRMS/MS; IC50 value; Monoamine oxidase inhibition; drugs of abuse; phenethylamines