Fluorine in psychedelic phenethylamines
Drug Testing and Analysis – February 28, 2012
Source: OpenAlex
Summary
Introducing fluorine into phenethylamines can significantly alter their psychoactive properties. An analysis of over 60 fluorinated phenethylamines revealed that while some compounds, like fluoroescaline, showed minimal psychoactivity, others such as trifluoromescaline demonstrated increased potency and duration compared to mescaline. Specifically, difluoromescaline and trifluoromescaline surpassed mescaline's effects, highlighting the potential of these designer drugs in pharmacology. With fluorinated compounds comprising 5-15% of successful pharmaceuticals, their impact on neurochemistry and behavior continues to gain attention across various fields.
Abstract
The so‐called psychedelic phenethylamines represent a class of drugs with a large range of psychoactive properties in humans, ranging from naturally occurring mescaline to amphetamine analogues and homologues. The interest in many of these compounds, occasionally referred to as designer‐drugs, is widely dispersed across popular culture and political and scientific communities. In recent decades, fluorine has become a powerful and important tool in medicinal chemistry. In addition, fluorine‐containing compounds and medicines can be found in numerous commercially successful pharmaceuticals that have gained a market share of some 5–15%. One might anticipate this trend to increase in the future. As far as fluorinated phenethylamines are concerned, much less is known about their chemistry and pharmacology. This paper provides an overview regarding the biological properties of over 60 fluorinated phenethylamines and discusses both historical and recent chemistry‐related developments. It was shown that the introduction of fluorine into the phenethylamine nucleus can impact greatly on psychoactivity of these compounds, ranging from marked loss to enhancement and prolongation of effects. For example, in contrast to the psychoactive escaline (70), it was observed that its fluoroescaline (76) counterpart was almost devoid of psychoactive effects. Difluoroescaline (77), on the other hand, retained, and trifluoroescaline (78) showed increased human potency of escaline (70). Difluoromescaline (72) and trifluoromescaline (73) increasingly surpassed human potency and duration of mescaline (22) effects. Copyright © 2012 John Wiley & Sons, Ltd.