The psychoactive aminoalkylbenzofuran derivatives, 5-APB and 6-APB, mimic the effects of 3,4-methylenedioxyamphetamine (MDA) on monoamine transmission in male rats.
Simon D Brandt, Hailey M Walters, John S Partilla, Bruce E Blough, Pierce V Kavanagh, Michael H Baumann
Psychopharmacology December 2020 DOI: 10.1007/s00213-020-05648-z (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical in vitro and in vivo experimental study Peer reviewed |
|---|---|
| Population | Male rats (in vitro rat brain synaptosomes and in vivo conscious male rats) |
| Interventions | 5-APB 6-APB 5-MAPB 6-MAPB MDA MDMA |
| Dose | 5-APB 0.3 and 1.0 mg/kg, i.v.; 6-APB 0.3 and 1.0 mg/kg, i.v.; MDA 1.0 and 3.0 mg/kg, i.v. |
| Duration | Behavioral activation assessed for at least 2 h post-injection |
| Keywords | Benzofury Designer drugs Locomotor activity MDMA, Mda Microdialysis Monoamine transporter Release Synthetic stimulants |
| Key findings | All four benzofuran derivatives were substrate-type releasers at DAT, NET, and SERT with nanomolar potency, and were at least threefold more potent than MDA and MDMA at evoking transporter-mediated release. In rats, 5-APB and 6-APB produced dose-related increases in extracellular dopamine and serotonin in the nucleus accumbens and sustained forward locomotion lasting at least 2 hours. The authors suggest these compounds may have abuse liability and pose risks, especially when combined with other drugs that enhance monoamine transmission. |
Abstract
The nonmedical use of new psychoactive substances (NPS) is a worldwide public health concern. The so-called "benzofury" compounds, 5-(2-aminopropyl)benzofuran (5-APB) and 6-(2-aminopropyl)benzofuran (6-APB), are NPS with stimulant-like properties in human users. These substances are known to interact with monoamine transporters and 5-HT receptors in transfected cells, but less is known about their effects in animal models. Here, we used in vitro monoamine transporter assays in rat brain synaptosomes to characterize the effects of 5-APB and 6-APB, together with their N-methyl derivatives 5-MAPB and 6-MAPB, in comparison with 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA). In vivo neurochemical and behavioral effects of 5-APB (0.3 and 1.0 mg/kg, i.v.) and 6-APB (0.3 and 1.0 mg/kg, i.v.) were assessed in comparison with MDA (1.0 and 3.0 mg/kg, i.v.) using microdialysis sampling in the nucleus accumbens of conscious male rats. All four benzofuran derivatives were substrate-type releasers at dopamine transporters (DAT), norepinephrine transporters (NET), and serotonin transporters (SERT) with nanomolar potencies, similar to the profile of effects produced by MDA and MDMA. However, the benzofurans were at least threefold more potent than MDA and MDMA at evoking transporter-mediated release. Like MDA, both benzofurans induced dose-related elevations in extracellular dopamine and serotonin in the brain, but benzofurans were more potent than MDA. The benzofuran derivatives also induced profound behavioral activation characterized by forward locomotion which lasted for at least 2 h post-injection. Overall, benzofurans are more potent than MDA in vitro and in vivo, producing sustained stimulant-like effects in rats. These data suggest that benzofuran-type compounds may have abuse liability and could pose risks for adverse effects, especially if used in conjunction with abused drugs or medications which enhance monoamine transmission in the brain.