benzofuran.svg) | |
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| Other names | 1-Benzofuran-5-ylpropan-2-amine |
| Routes of administration | Oral |
| Drug class | Serotonin–norepinephrine–dopamine releasing agent;Serotonin5-HT2 receptoragonist;Entactogen;Stimulant;Psychedelic |
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| Chemical and physical data | |
| Formula | C11H13NO |
| Molar mass | 175.231 g·mol−1 |
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5-APB, also known as5-(2-aminopropyl)benzofuran, is anentactogen of thephenethylamine,amphetamine, andbenzofuran families. 5-APB and related drugs have sometimes been informally called "Benzofury".
5-APB was first described in thescientific literature in 2000[2][3][4][5] and emerged as a noveldesigner drug in 2010.[3][4][6][7]
Users describe the effects of 5-APB as includingeuphoria among others.[3] Largely, its effects reported were similar to those of the drugMDMA but not as strong.[citation needed] The drug has been reported to producevisual disturbances and is said to have mildpsychedelic effects.[3][8]
Recreational use of 5-APB has been associated with death in combination with other drugs[9][10] and solely as the result of 5-APB.[11]
5-APB acts as aserotonin–norepinephrine–dopamine releasing agent (SNDRA), withEC50Tooltip half-maximal effective concentration values formonoamine release of 19 nM forserotonin, 21 nM fornorepinephrine, and 31 nM fordopamine in rat brainsynaptosomes.[6][12] It is also aserotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI).[6]
5-APB is a potentagonist of theserotonin5-HT2A and5-HT2B receptors.[6][12] ItsEC50Tooltip half-maximal effective concentration (EmaxTooltip maximal efficacy) values were 6,300 nM (54%) at the serotonin 5-HT2A receptor and 280 nM (61–92%) at the serotonin 5-HT2B receptor.[6][12] It also showsaffinity for the serotonin5-HT2C receptor (Ki = 880 nM) and the serotonin5-HT1A receptor (Ki = 3,300 nM).[6][12] It has been reported to act as an agonist of the serotonin 5-HT2C receptor similarly to the serotonin 5-HT2A and 5-HT2B receptors.[3][13] The drug's potent agonism of the serotonin 5-HT2B receptor makes it likely that 5-APB would becardiotoxic with long-term use, as seen with other serotonin 5-HT2B receptor agonists such asfenfluramine andMDMA.[citation needed]
5-APB also shows high affinity for the mouse and rattrace amine-associated receptor 1 (TAAR1).[6]
Inanimal studies, 5-APB produces robusthyperlocomotion, robustconditioned place preference (CPP) but limitedself-administration, fully substitutes forMDMA indrug discrimination tests, and partially substitutes forDOM,cocaine, andmethamphetamine in drug discrimination tests.[14]
5-APB, also known as 5-(2-aminopropyl)benzofuran, is aphenethylamine,amphetamine, andbenzofuran and ananalogue of3,4-methylenedioxyamphetamine (MDA).
5-APB is commonly found as thesuccinate andhydrochloridesalt. The hydrochloride salt is 10% morepotent by mass and doses should be adjusted accordingly.
Thechemical synthesis of 5-APB has been described.[5]
A forensic standard of 5-APB is available, and the compound has been posted on the Forendex website of potential drugs of abuse.[15] TheUS Department of Justice andDEA have also conducted studies concerning the detection of 5-APB.[16]
Analogues of 5-APB includeMDA,5-APDB,5-MAPB,6-APB,5-APBT, and5-API, among others.
5-APB, along with6-APB, was first described in thescientific literature by Karin Briner and colleagues atEli Lilly and Company in apatent in 2000.[2][3][4][5] They were specifically studied asserotonin5-HT2C receptoragonists for potential medical applications at this time.[2][3][4][5] The description of 5-APB and 6-APB in the literature had followed the earlier work on5-APDB and6-APDB asserotonin releasing agents andentactogens byDavid E. Nichols and colleagues atPurdue University in 1993.[4][6][17] 5-APB, along with 6-APB, emerged as a noveldesigner drug in 2010.[3][4][6][7] 5-APB and 6-APB are often confused with 5-APDB and 6-APDB.[4]
On March 5, 2014 the UK Home Office announced that 5-APB would be made a class B drug on 10 June 2014 alongside every other benzofuran entactogen and many structurally related drugs.[18]
The synthetic preparation of both 5-APB and 6-APB was first published in 2000 as part of a research program designed for the development of selective 5-HT2C receptor agonists (Briner et al. 2000; Briner et al. 2006), and the preparation of other isomers was reported for forensic purposes a decade later (Casale and Hays 2012; Stanczuk et al. 2013).
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.
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).
[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).
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.
5-APB ... has been implicated in 10 recent drug-related deaths in the UK
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
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