Wikipedia

6-APB

6-APB(6-(2-aminopropyl)benzofuran) is anempathogenicpsychoactive drugof thesubstituted benzofuranandsubstituted phenethylamineclasses.[1]6-APB andother compoundsare sometimes informally called "Benzofury" in newspaper reports. It issimilar in structuretoMDA,but differs in that the 3,4-methylenedioxyphenylringsystem has been replaced with abenzofuranring. 6-APB is also the unsaturated benzofuran derivative of6-APDB.It may appear as a tan grainy powder.[citation needed]

6-APB
Ball-and-stick model of the 6-APB molecule
Clinical data
Trade namesBenzofury.
Routes of
administration		By mouth,insufflation
Drug classEmpathogen–entactogen;Stimulant
ATC code
  • None
Legal status
Legal status
Pharmacokineticdata
Onset of action30–60 minutes
Duration of action7–10 hours
Identifiers
  • 1-(1-Benzofuran-6-yl)propan-2-amine
CAS Number
PubChemCID
ChemSpider
UNII
CompTox Dashboard(EPA)
Chemical and physical data
FormulaC11H13NO
Molar mass175.231g·mol−1
3D model (JSmol)
  • NC(C)CC1=CC(OC=C2)=C2C=C1
  • InChI=1S/C11H13NO/c1-8(12)6-9-2-3-10-4-5-13-11(10)7-9/h2-5,7-8H,6,12H2,1H3checkY
  • Key:FQDAMYLMQQKPRX-UHFFFAOYSA-NcheckY
☒NcheckY(what is this?)(verify)

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]

Pharmacology

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Small clumps of 6-APB powder

Pharmacodynamics

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6-APB is aserotonin–norepinephrine–dopamine reuptake inhibitor(SNDRI) with Kivalues of 117, 150, and 2698 nM for thenorepinephrine transporter(NET),dopamine transporter(DAT), andserotonin transporter(SERT), respectively.[1]In addition, 6-APB not onlyblocksthereuptakeof thesemonoamine neurotransmittersbut is also areleasing agentof them; that is, it is aserotonin-norepinephrine-dopamine releasing agent(SNDRA).[2]

In addition to actions at themonoamine transporters,6-APB is apotentfull agonistof theserotonin5-HT2Breceptor(Ki= 3.7 nM),[1]with higheraffinityfor thistargetthan any other site.[3]Moreover, unlikeMDMA,6-APB shows 100-foldselectivityfor the 5-HT2Breceptor over the5-HT2Aand5-HT2Creceptors.[3][4]It is notably both more potent and more selective as an agonist of the 5-HT2Breceptor than the reference 5-HT2Breceptor agonist,BW-723C86,which is commonly used for research into the 5-HT2Breceptor.[citation needed]Aside from the 5-HT2Breceptor, 6-APB has also been found to bind with high affinity to theα2C-adrenergic receptorsubtype (Ki= 45 nM), although the clinical significance of this action is unknown.[1]6-APB showed little other affinity at a wide selection of other sites.[1]

The potent agonism of the 5-HT2Breceptor makes it likely that 6-APB would becardiotoxicwith chronic or long-term use, as seen with other 5-HT2Breceptor agonists such as thewithdrawnserotonergicanorecticfenfluramine.[1][5]

Pharmacokinetics

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Thepharmacokineticsof 6-APB have not been studied, however, some information can be extracted from user reports. These suggest a slow onset of 40–120 minutes. The drugs peak effects last 7 hours, followed by a comedown phase of approximately 2 hours, and after effects for up to 24 hours.[6]

Metabolism

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Although limited literature is available, there is some data onmetabolismof 6-APB in rats. Its Phase I metabolism involveshydroxylationof thefuranring, then cleavage of the ring, followed by areductionof the unsaturatedaldehydefrom the previous step. The resulting aldehyde may then take two paths. It is either oxidized to acarboxylic acidor reduced to analcohol,and thenhydroxylated.Phase II metabolism consists ofglucuronidation.The most prevalent metabolites in rats were3-carboxymethyl-4-hydroxyamphetamineand4-carboxymethyl-3-hydroxyamphetamine.[7]

Adverse effects

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Acutepsychosishas been associated with recreational use of 6-APB in combination with the synthetic cannabinoid JWH-122.[8]

Reagents results

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6-APB and its structural isomer5-APBhave been tested with a series of agents including:Marquis,Liebermann,Mecke,andFroehdereagents.[9]Exposing compounds to the reagents gives a colour change which is indicative of the compound under test.

Compound Marquis Mecke Mandelin Liebermann Froehde Gallic Ehrlich Hofmann Simon's Folin
6-APB Purple Purple to black Purple to black Black Purple Brown Orange Light orange No reaction Light orange
6-APB succinate Purple Purple to black Purple to black Black Purple Brown Faint orange No reaction No reaction Light orange

6-APB succinate is reported to be practically insoluble inCHCl3as well as very minimally soluble in coldwater.A batch seized by the DEA contained a 2:1 ratio of succinate to 6-APB.[10]

Synthesis

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Synthesis of 6-APB and its structural isomer 4-APB[10]

The synthesis by Brineret al.[4]entailed reflu xing3-bromophenolwith bromoacetaldehyde diethylacetal andsodium hydrideto give the diethylacetal,which then was heated withpolyphosphoric acidto 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 pairsfor further examination.

Dosage and duration

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6-APB can be found infreebase,hydrochloride,andsuccinateform. The freebase is purportedly 20% stronger than thehydrochloride saltand 65% stronger than the succinate. This means 100 mg of 6-APB HCl is equivalent to 83 mg of 6-APB freebase and 100 mg of 6-APB succinate is equivalent to 60 mg of 6-APB freebase. Different production batches may have impurities and should be treated with care.[citation needed]

Based on anecdotal reports, the dosages for 6-APB hydrochloride are the following:

Dosage
Oral
Threshold 15 mg
Light 15–60 mg
Common 60–90 mg
Strong 90–120 mg
Heavy 120 mg +
Duration
Oral
Onset 30–60 minutes (or more)
Come up 60–120 minutes
Peak 3–4 hours
Offset 2–3 hours
Total 7–10 hours
After effects 6–48 hours

The dosages for freebases or succinates have to be adjusted accordingly.

Law

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North America

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Canada

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In 1999, amphetamines were changed fromSchedule IIItoSchedule Ias a result of theSafe Streets Act.Some have speculated that 6-APB's structure qualifies it as a Schedule I drug as ananalogof MDA.[11][unreliable source?]

In 2014, a study funded by theCanadian Institutes of Health Researchnoted that 6-APB "may or may not be legal in Canada depending on how one interprets the current Act"[12]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'sbenzofuranstructure does not make it a direct analogue ofamphetaminedespite similarities in effects.

United States

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6-APB is not scheduled at the federal level in theUnited States,[13][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.[14]

Finland

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6-APB is scheduled in government decree on narcotic substances, preparations and plants and hence is illegal.[15]

France

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6-APB is illegal inFrance.[16]

Germany

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6-APB is illegal inGermanysince the 17th of July, 2013, when it was added toAnlage IIof theBetäubungsmittelgesetz.[citation needed]

Italy

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6-APB is illegal inItaly.[17]

Luxembourg

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InLuxembourg,6-APB is not cited in the list of prohibited substances.[18]Therefore, it is still a legal substance.

Netherlands

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6-APB is not listed under theOpium Lawor the Medicine Act in theNetherlands,and thus currently legal.[citation needed]

New Zealand and Australia

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Certain countries contain a "substantially similar" catch-all clause in their drug law, such asNew ZealandandAustralia.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.[19]

Sweden

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InSweden,as of 27 December 2009 6-APB is classified as "health hazard" under the actLagen om förbud mot vissa hälsofarliga varor(translatedAct on the Prohibition of Certain Goods Dangerous to Health).[20]

UK

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On June 10, 2013 6-APB and a number of analogues were classified asTemporary Class Drugsin the UK following an ACMD recommendation.[5]This means that sale and import of the named substances are criminal offences and are treated as for class B drugs.[21]On November 28, 2013 the ACMD recommended that 6-APB and related benzofurans should becomeClass B,Schedule 1substances.[5]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.[22]

China

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6-APB has been a controlled substance in China since 1 July 2024[23]

See also

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References

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  1. ^abcdefIversen L, Gibbons S, Treble R, Setola V, Huang XP,Roth BL(January 2013)."Neurochemical profiles of some novel psychoactive substances".European Journal of Pharmacology.700(1–3):147–51.doi:10.1016/j.ejphar.2012.12.006.PMC3582025.PMID23261499.
  2. ^Rickli A, Kopf S, Hoener MC, Liechti ME (July 2015)."Pharmacological profile of novel psychoactive benzofurans".British Journal of Pharmacology.172(13):3412–25.doi:10.1111/bph.13128.PMC4500375.PMID25765500.
  3. ^abCanal CE, Murnane KS (January 2017)."2C receptor and the non-addictive nature of classic hallucinogens".Journal of Psychopharmacology.31(1):127–143.doi:10.1177/0269881116677104.PMC5445387.PMID27903793.
  4. ^abUS 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.
  5. ^abcBrowne J (4 June 2013)."Temporary class drug order on benzofury and NBOMe compounds - letter from ACMD".Advisory Council on the Misuse of Drugs.GOV.UK.
  6. ^Shaun L. Greene (2013).Novel Psychoactive Substances: Classification, Pharmacology and Toxicology Chapter 16 – Benzofurans and Benzodifurans.Boston: Academic Press. pp.383–392.doi:10.1016/B978-0-12-415816-0.00016-X.ISBN978-0-12-415816-0.
  7. ^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.
  8. ^Chan WL, Wood DM, Hudson S, Dargan PI (September 2013)."Acute psychosis associated with recreational use of benzofuran 6-(2-aminopropyl)benzofuran (6-APB) and cannabis".Journal of Medical Toxicology.9(3):278–81.doi:10.1007/s13181-013-0306-y.PMC3770991.PMID23733714.
  9. ^"Results".PRO Test.Retrieved2021-06-01.
  10. ^abCasale JF, Hays PA (January 2012)."The Characterization of 6-(2-Aminopropyl)benzofuran and Differentiation from its 4-, 5-, and 7-Positional Analogues"(PDF).Microgram Journal.9(2):61–74. Archived fromthe original(PDF)on 2016-11-05.Retrieved2016-06-08.
  11. ^"Controlled Drugs and Substances Act: Definitions and Interpretations".isomerdesign.Retrieved2019-11-11.
  12. ^Hudson AL, Lalies MD, Baker GB, Wells K, Aitchison KJ (2014-04-16)."Ecstasy, legal highs and designer drug use: A Canadian perspective".Drug Science, Policy and Law.1:2050324513509190.doi:10.1177/2050324513509190.ISSN2050-3245.S2CID159675835.
  13. ^"21 CFR — SCHEDULES OF CONTROLLED SUBSTANCES §1308.11 Schedule I."Archived fromthe originalon 2009-08-27.Retrieved2018-04-10.
  14. ^Casale JF, Hays PA (January 2011)."The characterization of 5-and 6-(2-aminopropyl)-2, 3-dihydrobenzofuran".Microgram J.8(2):62–74.
  15. ^"Ajantasa".finlex.fi.
  16. ^"Arrêté du 22 février 1990 fixant la liste des substances classées comme stupéfiants".
  17. ^"Nuove tabelle delle sostanze stupefacenti e psicotrope (DPR 309/90)"(PDF)(in Italian). Ministero della Salute. Archived fromthe original(PDF)on 2016-02-06.Retrieved2016-05-31.
  18. ^"Loi du 19 février 1973 concernant la vente de substances médicamenteuses et la lutte contre la toxicomanie. - Legilux".legilux.public.lu.Retrieved2021-06-01.
  19. ^"Misuse of Drugs Act 1975".New Zealand Legislation. 7 November 2015.
  20. ^"Förordning (1999:58) om förbud mot vissa hälsofarliga varor"(in Swedish). Lagbevakning med Notisum och Rättsnätet. 24 November 2009. Archived fromthe originalon 4 October 2013.Retrieved15 September2013.
  21. ^Browne J (4 June 2013)."'NBOMe' and 'Benzofury' banned ".Home Office.GOV.UK.
  22. ^UK Home Office (28 April 2014)."The Misuse of Drugs Act 1971 (Ketamine etc.) (Amendment) Order 2014".The National Archives.
  23. ^National Medical Products Administration (NMPA) of China (July 22, 2024)."Về đem xú phê chờ 46 loại vật chất xếp vào 《 phi dược dùng loại gây tê dược phẩm cùng tinh thần dược phẩm quản chế chủng loại tăng thêm mục lục 》 thông cáo".
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