Interactions of phenethylamine-derived psychoactive substances of the 2C-series with human monoamine oxidases.

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 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.

• Authors: Lea Wagmann, Simon D Brandt, Alexander Stratford, Hans H Maurer, Markus R Meyer
• Journal: Drug testing and analysis (Drug Test Anal) Vol. 11 Issue 2 Pg. 318-324 (Feb 2019) ISSN: 1942-7611 [Electronic] England
• PMID: 30188017 (Publication Type: Journal Article)
• Copyright: © 2018 John Wiley & Sons, Ltd.

Chemical References

• Designer Drugs
• Monoamine Oxidase Inhibitors
• Phenethylamines
• phenethylamine
• Monoamine Oxidase

Topics

• Designer Drugs (pharmacology)
• Humans
• In Vitro Techniques
• Inhibitory Concentration 50
• Molecular Structure
• Monoamine Oxidase (metabolism)
• Monoamine Oxidase Inhibitors (chemistry, pharmacology)
• Phenethylamines (chemistry, pharmacology)