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Pharmacological profile of novel psychoactive benzofurans

Anna Rickli, Simone Kopf, Marius C. Hoener, Matthias E. Liechti

British Journal of Pharmacology March 13, 2015 DOI: 10.1111/bph.13128 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics In vitro experimental study Peer reviewed
Population HEK 293 cells expressing human noradrenaline, dopamine, or serotonin uptake transporters
Topics MDMA
Keywords Monoamine neurotransmitter Pharmacology Receptor Dopamine Methamphetamine
Citations 115
Key findings Benzofurans act as indirect monoamine agonists that interact with transporters similarly to MDMA, but also activate 5-HT2B receptors, posing a risk for heart valve fibrosis.

Abstract

Background and Purpose Benzofurans are newly used psychoactive substances, but their pharmacology is unknown. The aim of the present study was to pharmacologically characterize benzofurans in vitro . Experimental Approach We assessed the effects of the benzofurans 5‐ APB , 5‐ APDB , 6‐ APB , 6‐ APDB , 4‐ APB , 7‐ APB , 5‐ EAPB and 5‐ MAPDB and benzodifuran 2 C ‐ B ‐ FLY on the human noradrenaline ( NA ), dopamine and 5‐ HT uptake transporters using HEK 293 cells that express the respective transporters. We also investigated the release of NA , dopamine and 5‐ HT from monoamine‐preloaded cells, monoamine receptor‐binding affinity and 5‐ HT 2A and 5‐ HT 2B receptor activation. Key Results All of the benzofurans inhibited NA and 5‐ HT uptake more than dopamine uptake, similar to methylenedioxymethamphetamine ( MDMA ) and unlike methamphetamine. All of the benzofurans also released monoamines and interacted with trace amine‐associated receptor 1 ( TA 1 receptor), similar to classic amphetamines. Most benzofurans were partial 5‐ HT 2A receptor agonists similar to MDMA , but also 5‐ HT 2B receptor agonists, unlike MDMA and methamphetamine. The benzodifuran 2 C ‐ B ‐ FLY very potently interacted with 5‐ HT 2 receptors and also bound to TA 1 receptors. Conclusions and Implications Despite very similar structures, differences were found in the pharmacological profiles of different benzofurans and compared with their amphetamine analogues. Benzofurans acted as indirect monoamine agonists that interact with transporters similarly to MDMA . The benzofurans also interacted with 5‐HT receptors. This pharmacological profile probably results in MDMA ‐like entactogenic psychoactive properties. However, benzofurans induce 5‐ HT 2B receptor activation associated with heart valve fibrosis. The pharmacology of 2 C ‐ B ‐ FLY indicates predominant hallucinogenic properties and a risk for vasoconstriction.

Comparable studies

Other preclinical and animal studies on MDMA, most cited first.

Study Year Design Participants
Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) 1987 Experimental study
3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain 1987 Animal experiment
Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells 2006 In vitro laboratory study
Small Changes in Ambient Temperature Cause Large Changes in 3,4-Methylenedioxymethamphetamine (MDMA)-Induced Serotonin Neurotoxicity and Core Body Temperature in the Rat Rats 1998 Experimental study
Altered Serotonin Innervation Patterns in the Forebrain of Monkeys Treated with (±)3,4-Methylenedioxymethamphetamine Seven Years Previously: Factors Influencing Abnormal Recovery Squirrel monkeys treated with MDMA 1999 Observational cohort

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