The effects of benzofury (5-APB) on the dopamine transporter and 5-HT2-dependent vasoconstriction in the rat.
Patrick Dawson, Jolanta Opacka-Juffry, James D Moffatt, Yusuf Daniju, Neelakshi Dutta, John Ramsey, Colin Davidson
Progress in Neuro-Psychopharmacology and Biological Psychiatry January 3, 2014 DOI: 10.1016/j.pnpbp.2013.08.013 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro pharmacological study Peer reviewed |
|---|---|
| Population | Rat brain tissue (autoradiography), rat accumbens brain slices, rat aorta, and rat stomach fundus |
| Intervention | 5-APB |
| Topics | LSD MDMA Serotonin |
| Keywords | 3,4, methylenedioxymethamphetamine 3,4-methylenedioxyamphetamine 5-2-aminopropylbenzofuran 5-apb 5-ht2 Acmd Auc Accumbens Benzofury Dopamine transporter Mda Pfc Prefrontal cortex Roi Vasoconstriction Acsf Artificial cerebrospinal fluid Region of interest |
| Key points | 5-APB displaced ligands from the dopamine transporter and 5-HT2 receptors, slowed dopamine reuptake and at high concentrations caused reverse dopamine transport in rat accumbens slices, and contracted rat aorta and stomach fundus via 5-HT2A and 5-HT2B receptors. The authors argue this profile is consistent with stimulant and hallucinogenic properties and suggest 5-HT2B activity may cause cardiotoxicity. |
Abstract
5-APB, commonly marketed as 'benzofury' is a new psychoactive substance and erstwhile 'legal high' which has been implicated in 10 recent drug-related deaths in the UK. This drug was available on the internet and in 'head shops' and was one of the most commonly sold legal highs up until its recent UK temporary ban (UK Home Office). Despite its prominence, very little is known about its pharmacology. This study was undertaken to examine the pharmacology of 5-APB in vitro. We hypothesised that 5-APB would activate the dopamine and 5-HT systems which may underlie its putative stimulant and hallucinogenic effects. Autoradiographic studies showed that 5-APB displaced both [(125)I] RTI-121 and [(3)H] ketanserin from rat brain tissue suggesting affinity at the dopamine transporter and 5-HT2 receptor sites respectively. Voltammetric studies in rat accumbens brain slices revealed that 5-APB slowed dopamine reuptake, and at high concentrations caused reverse transport of dopamine. 5-APB also caused vasoconstriction of rat aorta, an effect antagonised by the 5-HT2A receptor antagonist ketanserin, and caused contraction of rat stomach fundus, which was reversed by the 5-HT2B receptor antagonist RS-127445. These data show that 5-APB interacts with the dopamine transporter and is an agonist at the 5-HT2A and 5-HT2B receptors in the rat. Thus 5-APB's pharmacology is consistent with it having both stimulant and hallucinogenic properties. In addition, 5-APB's activity at the 5-HT2B receptor may cause cardiotoxicity.
Comparable studies
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| Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) | 1987 | Experimental study | |
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| 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 |
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