title: The effects of benzofury (5-APB) on the dopamine transporter and 5-HT2-dependent vasoconstriction in the rat.
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.
authors.affiliation: Pharmacology and Cell Physiology, Division of Biomedical Science, St George's University of London, London SW17 0RE, United Kingdom.
authors.forename: Patrick
authors.initials: P
authors.lastname: Dawson
authors.forename: Jolanta
authors.initials: J
authors.lastname: Opacka-Juffry
authors.forename: James D
authors.initials: JD
authors.lastname: Moffatt
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Daniju
authors.forename: Neelakshi
authors.initials: N
authors.lastname: Dutta
authors.forename: John
authors.initials: J
authors.lastname: Ramsey
authors.forename: Colin
authors.initials: C
authors.lastname: Davidson
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001572:Benzofurans / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003042:Cocaine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D004298:Dopamine / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007456:Iodine Isotopes / Q000493:pharmacokinetics; D007650:Ketanserin / Q000493:pharmacokinetics; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology; D011437:Propylamines / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D044348:Receptors, Serotonin, 5-HT2 / Q000378:metabolism*; D018490:Serotonin Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D014316:Tritium / Q000493:pharmacokinetics; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D001572:Benzofurans; D050483:Dopamine Plasma Membrane Transport Proteins; D007456:Iodine Isotopes; D011437:Propylamines; D044348:Receptors, Serotonin, 5-HT2; D018490:Serotonin Agents; D014316:Tritium; C079213:RTI 121; C587038:6-(2-aminopropyl)benzofuran; D007650:Ketanserin; D003042:Cocaine; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D004298:Dopamine
keywords: 3,4, methylenedioxymethamphetamine; 3,4-methylenedioxyamphetamine; 5-(2-aminopropyl)benzofuran; 5-APB; 5-HT(2); ACMD; AUC; Accumbens; Advisory Council on the Misuse of Drugs; Benzofury; DA; Dopamine transporter; LSD; MDA; MDMA; PFC; Prefrontal cortex; ROI; Vasoconstriction; aCSF; area under the curve; artificial cerebrospinal fluid; dopamine; lysergic acid diethylamide; prefrontal cortex; region of interest