While the drug never became particularly popular, it briefly entered the rave and underground clubbing scene in the UK before its sale and import were banned. It falls under the category ofresearch chemicals, sometimes called "legal highs” if uncontrolled. Because 6-APB and other substituted benzofurans have not been explicitly outlawed in some countries, they are often technically legal, contributing to its popularity.[citation needed]
Besides the serotonin 5-HT2 receptors, 6-APB has been found to bind with high affinity to theα2C-adrenergic receptor (Ki = 45nM), although the significance of this action in humans is unknown.[1] 6-APB showed little other affinity at a wide selection of other sites, with some exceptions like the rodenttrace amine-associated receptor 1 (TAAR1).[1][6]
The potent agonism of the serotonin 5-HT2B receptor makes it likely that 6-APB would becardiotoxic with chronic or long-term use, as seen with other serotonin 5-HT2B receptor agonists such as thewithdrawnserotonergicanorecticfenfluramine.[1][11]
Thepharmacokinetics of 6-APB have not been studied, however, some information can be extracted from user reports.[3] These suggest a slow onset of 40 to 120minutes.[3] The drugs peak effects last 7hours, followed by a comedown phase of approximately 2hours, and after effects for up to 24hours.[3]
Synthesis of 6-APB and its structural isomer 4-APB[13]
Thechemical synthesis of 6-APB has been described.[5] The synthesis by Briner and colleagues[5] entailed refluxing3-bromophenol with bromoacetaldehyde diethylacetal andsodium hydride to give the diethylacetal, which then was heated withpolyphosphoric acid to give a mixture of bromobenzofuranstructural isomers: 4-bromo-1-benzofuran and 6-bromo-1-benzofuran. The isomers were separated bysilica gelcolumn chromatography, then converted to their respective propanone derivatives, and then reductively aminated to give 6-APB and 4-APB, both of which were converted to theirHClion pairs for further examination.
6-APB and its structural isomer5-APB have been tested with a series of agents including:Marquis,Liebermann,Mecke, andFroehde reagents.[14] Exposing compounds to the reagents gives a colour change which is indicative of the compound under test.
6-APB succinate is reported to be practically insoluble inCHCl3 as well as very minimally soluble in coldwater. A batch seized by the DEA contained a 2:1 ratio of succinate to 6-APB.[13]
In 2014, a study funded by theCanadian Institutes of Health Research noted that 6-APB "may or may not be legal in Canada depending on how one interprets the current Act"[17] and that it could be purchased for academic purposes without an exemption from Health Canada. The study also noted how, unlike the MDMA it often serves as a replacement for in countries like the US, 6-APB'sbenzofuran structure does not make it a direct analogue ofamphetamine despite similarities in effects.
6-APB, as well as multiple substances based on the phenylethamine structure, like most cathinones and amphetamines, are banned under theOpium Law since July 1st, 2025,[23] following an amendment to deal with New Psychoactive Substances (NPS) in theNetherlands. Since this is a structural ban instead of a direct one, later substances that differ slightly but use the same skeleton will also be preemptively banned.
Certain countries contain a "substantially similar" catch-all clause in their drug law, such asNew Zealand andAustralia. This includes 6-APB as it is similar in chemical structure to the class A drugMDA, meaning 6-APB may be viewed as a controlled substance analogue in these jurisdictions.[24]
On June 10, 2013 6-APB and a number of analogues were classified asTemporary Class Drugs in the UK following an ACMD recommendation.[11] This means that sale and import of the named substances are criminal offences and are treated as for class B drugs.[27] On November 28, 2013 the ACMD recommended that 6-APB and related benzofurans should becomeClass B,Schedule 1 substances.[11] On March 5, 2014 the UK Home Office announced that 6-APB would be made a class B drug on 10 June 2014 alongside every other benzofuran entactogen and many structurally related drugs.[28]
6-APB is not scheduled at the federal level in theUnited States,[29][failed verification] but it may be considered an analog of amphetamine, in which case purchase, sale, or possession could be prosecuted under theFederal Analog Act.[30]
^abcdefghijGreene SL (2013). "Benzofurans and Benzodifurans".Novel Psychoactive Substances. Elsevier. pp. 383–392.doi:10.1016/b978-0-12-415816-0.00016-x.ISBN978-0-12-415816-0. Retrieved15 April 2025.A patent granted to Eli Lilly and Company in 2006 classifies 5-APB and 6-APB as 5HT2C receptor agonists [15]. [...] Internet user reports of 5-APB and 6-APB date from late 2010 [13]. [...] [15] Briner K, Burkhart JP, Burkholder TM, et al. Aminoalkylbenzofurans as serotonin (5-HT(2c)) agonists. 7045545 (US patent). Published 2000-01-19, issued 2006-16-03.
^abcdefgRoque Bravo R, Carmo H, Carvalho F, Bastos ML, Dias da Silva D (August 2019). "Benzo fury: A new trend in the drug misuse scene".J Appl Toxicol.39 (8):1083–1095.doi:10.1002/jat.3774.PMID30723925.The first benzofurans appearing on the drug scene in 2010‐11, were 5‐(2‐aminopropyl) benzofuran (5‐APB) and 6‐(2‐aminopropyl) benzofuran (6‐APB). These compounds had been previously patented in 2006 as potential therapeutic drugs for eating disorders and seizures, due to their action as serotonergic agonists (Advisory Council on the Misuse of Drugs, 2013; Taschwer, Hofer, & Schmid, 2014). While these first two molecules are the subject of most published investigations, namely those concerning pharmacological aspects, other benzofuran analogues have also been marketed as "legal highs." Examples of such analogues are 5‐(2‐ aminopropyl)‐2,3‐dihydrobenzofuran (5‐APDB) and 6‐(2‐aminopropyl)‐ 2,3‐dihydrobenzofuran (6‐APDB), first synthesized in 1993, purportedly as non‐neurotoxic benzofuran analogues of 3,4‐methylenedioxyamphetamine (MDA) (Monte, Marona‐Lewicka, Cozzi, & Nichols, 1993). These drugs are often confused with 5‐APB and 6‐APB (Casale, 2012; Casale & Hays, 2011).
^abcdefUS patent 7045545, Briner K, Burkhart JP, Burkholder TP, Fisher MJ, Gritton WH, Kohlman DT, Liang SX, Miller SC, Mullaney JT, Xu YC, Xu Y, "Aminoalkylbenzofurans as serotonin (5-HT(2c)) agonists", published 19 January 2000, issued 16 May 2006, assigned to Eli Lilly Co.
^abcdefgRickli A, Kopf S, Hoener MC, Liechti ME (July 2015)."Pharmacological profile of novel psychoactive benzofurans".British Journal of Pharmacology.172 (13):3412–3425.doi:10.1111/bph.13128.PMC4500375.PMID25765500.[5-APB] and [6-APB] are benzofuran analogues of MDA (Figure 1). [5-APDB] and [6-APDB] are dihydrobenzofuran analogues (Figure 1) that were originally synthesized for research purposes (Monte et al., 1993). [...] 5-APB and 6-APB appeared on the drug market in 2010– 2011 (Chan et al., 2013; Jebadurai et al., 2013; Stanczuk et al., 2013; Archer et al., 2014; Elliott and Evans, 2014; King, 2014), with reports of intoxication (Chan et al., 2013; Greene, 2013; Jebadurai et al., 2013; Seetohul and Pounder, 2013).
^Canal CE (2018). "Serotonergic Psychedelics: Experimental Approaches for Assessing Mechanisms of Action".New Psychoactive Substances. Handbook of Experimental Pharmacology. Vol. 252. Cham: Springer International Publishing. pp. 227–260.doi:10.1007/164_2018_107.ISBN978-3-030-10560-0.PMC6136989.PMID29532180.Despite micromolar 5-HT1A affinities (Rickli et al. 2015b), Nbenzylphenethylamines retain potent psychedelic effects. Also, benzofurans, such as 5-APB and 6-APB, are potent and efficacious 5-HT2B agonists but have very low potency at 5-HT2A receptors. They also stimulate efflux of DA and 5-HT and have activity at TAAR1 receptors (Iversen et al. 2013; Rickli et al. 2015a), but anecdotal reports note that psychedelic effects are relatively minor compared to classic psychedelics. These observations provide further credence that the 5-HT2A receptor, but not 5-HT1A, 5-HT2B, TAAR1, or monoamine transporters, initiates psychedelic effects.
^Nugteren-van Lonkhuyzen JJ, van Riel AJ, Brunt TM, Hondebrink L (December 2015). "Pharmacokinetics, pharmacodynamics and toxicology of new psychoactive substances (NPS): 2C-B, 4-fluoroamphetamine and benzofurans".Drug and Alcohol Dependence.157:18–27.doi:10.1016/j.drugalcdep.2015.10.011.PMID26530501.
^Luethi D, Liechti ME (April 2020)."Designer drugs: mechanism of action and adverse effects".Arch Toxicol.94 (4):1085–1133.doi:10.1007/s00204-020-02693-7.PMC7225206.PMID32249347.Some benzofuran designer drugs were originally investigated as part of a study that examined the role of ring oxygen atoms in interactions between MDA and monoamine transporters (Monte et al. 1993). [...] Monte AP, Marona-Lewicka D, Cozzi NV, Nichols DE (1993) Synthesis and pharmacological examination of benzofuran, indan, and tetralin analogues of 3,4-(methylenedioxy)amphetamine. J Med Chem 36(23):3700–3706.https://doi.org/10. 1021/jm00075a027{{cite journal}}:External link in|quote= (help)
Notes: (1) TAAR1 activity of ligands varies significantly between species. Some agents that are TAAR1 ligands in some species are not in other species. This navbox includes all TAAR1 ligands regardless of species. (2) See the individual pages for references, as well as theList of trace amines,TAAR, andTAAR1 pages. See also:Receptor/signaling modulators
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