6-APB

Last updated

6-APB
6APB.svg
6-APB molecule ball.png
Clinical data
Routes of
administration 		By mouth, insufflation
Drug class Empathogen–entactogen; Stimulant
ATC code
  • None
Legal status
Legal status
Pharmacokinetic data
Onset of action 30–60 minutes
Duration of action 7–10 hours
Identifiers
  • 1-(1-Benzofuran-6-yl)propan-2-amine
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
Formula C11H13NO
Molar mass 175.231 g·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,6,12H2,1H3 Yes check.svgY
  • Key:FQDAMYLMQQKPRX-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

6-APB (6-(2-aminopropyl)benzofuran) is an empathogenic psychoactive drug of the substituted benzofuran and substituted phenethylamine classes. [1] 6-APB and other compounds are sometimes informally called "Benzofury" in newspaper reports. It is similar in structure to MDA, but differs in that the 3,4-methylenedioxyphenyl ring system has been replaced with a benzofuran ring. 6-APB is also the unsaturated benzofuran derivative of 6-APDB. It may appear as a tan grainy powder.[ citation needed ]

Contents

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 of research 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

Small clumps of 6-APB powder 6-APB.jpg
Small clumps of 6-APB powder

Pharmacodynamics

6-APB is a serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI) with Ki values of 117, 150, and 2698 nM for the norepinephrine transporter (NET), dopamine transporter (DAT), and serotonin transporter (SERT), respectively. [1] In addition, 6-APB not only blocks the reuptake of these monoamine neurotransmitters but is also a releasing agent of them; that is, it is a serotonin-norepinephrine-dopamine releasing agent (SNDRA). [2]

In addition to actions at the monoamine transporters, 6-APB is a potent full agonist of the serotonin 5-HT2B receptor (Ki = 3.7 nM), [1] with higher affinity for this target than any other site. [3] Moreover, unlike MDMA, 6-APB shows 100-fold selectivity for the 5-HT2B receptor over the 5-HT2A and 5-HT2C receptors. [3] [4] It is notably both more potent and more selective as an agonist of the 5-HT2B receptor than the reference 5-HT2B receptor agonist, BW-723C86, which is commonly used for research into the 5-HT2B receptor.[ citation needed ] Aside from the 5-HT2B receptor, 6-APB has also been found to bind with high affinity to the α2C-adrenergic receptor subtype (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-HT2B receptor makes it likely that 6-APB would be cardiotoxic with chronic or long-term use, as seen with other 5-HT2B receptor agonists such as the withdrawn serotonergic anorectic fenfluramine. [1] [5]

Pharmacokinetics

The pharmacokinetics of 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

Although limited literature is available, there is some data on metabolism of 6-APB in rats. Its Phase I metabolism involves hydroxylation of the furan ring, then cleavage of the ring, followed by a reduction of the unsaturated aldehyde from the previous step. The resulting aldehyde may then take two paths. It is either oxidized to a carboxylic acid or reduced to an alcohol, and then hydroxylated. Phase II metabolism consists of glucuronidation. The most prevalent metabolites in rats were 3-carboxymethyl-4-hydroxyamphetamine and 4-carboxymethyl-3-hydroxyamphetamine. [7]

Adverse effects

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

Reagents results

6-APB and its structural isomer 5-APB have been tested with a series of agents including: Marquis, Liebermann, Mecke, and Froehde reagents. [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-APBPurplePurple to blackPurple to blackBlackPurpleBrownOrangeLight orangeNo reactionLight orange
6-APB succinatePurplePurple to blackPurple to blackBlackPurpleBrownFaint orangeNo reactionNo reactionLight orange

6-APB succinate is reported to be practically insoluble in CHCl3 as well as very minimally soluble in cold water. A batch seized by the DEA contained a 2:1 ratio of succinate to 6-APB. [10]

Synthesis

Synthesis of 6-APB and its structural isomer 4-APB Synthesis of 6-APB and its structural isomer 4-APB.png
Synthesis of 6-APB and its structural isomer 4-APB

The synthesis by Briner et al. [4] entailed refluxing 3-bromophenol with bromoacetaldehyde diethylacetal and sodium hydride to give the diethyl acetal, which then was heated with polyphosphoric acid to give a mixture of bromobenzofuran structural isomers: 4-bromo-1-benzofuran and 6-bromo-1-benzofuran. The isomers were separated by silica gel column 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 their HCl ion pairs for further examination.

Dosage and duration

6-APB can be found in freebase, hydrochloride, and succinate form. The freebase is purportedly 20% stronger than the hydrochloride salt and 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
Threshold15 mg
Light15–60 mg
Common60–90 mg
Strong90–120 mg
Heavy120 mg +
Duration
Oral
Onset30–60 minutes (or more)
Come up60–120 minutes
Peak3–4 hours
Offset2–3 hours
Total7–10 hours
After effects6–48 hours

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

Law

North America

Canada

In 1999, amphetamines were changed from Schedule III to Schedule I as a result of the Safe Streets Act. Some have speculated that 6-APB's structure qualifies it as a Schedule I drug as an analog of MDA. [11] [ unreliable source? ]

In 2014, a study funded by the Canadian Institutes of Health Research noted 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's benzofuran structure does not make it a direct analogue of amphetamine despite similarities in effects.

United States

6-APB is not scheduled at the federal level in the United States, [13] [ failed verification ] but it may be considered an analog of amphetamine, in which case purchase, sale, or possession could be prosecuted under the Federal Analog Act. [14]

Finland

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

France

6-APB is illegal in France. [16]

Germany

6-APB is illegal in Germany since the 17th of July, 2013, when it was added to Anlage II of the Betäubungsmittelgesetz.[ citation needed ]

Italy

6-APB is illegal in Italy. [17]

Luxembourg

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

Netherlands

6-APB is not listed under the Opium Law or the Medicine Act in the Netherlands, and thus currently legal.[ citation needed ]

New Zealand and Australia

Certain countries contain a "substantially similar" catch-all clause in their drug law, such as New Zealand and Australia. This includes 6-APB as it is similar in chemical structure to the class A drug MDA, meaning 6-APB may be viewed as a controlled substance analogue in these jurisdictions. [19]

Sweden

In Sweden, as of 27 December 2009 6-APB is classified as "health hazard" under the act Lagen om förbud mot vissa hälsofarliga varor (translated Act on the Prohibition of Certain Goods Dangerous to Health). [20]

UK

On June 10, 2013 6-APB and a number of analogues were classified as Temporary Class Drugs in 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 become Class B, Schedule 1 substances. [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

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

Related Research Articles

α-Methyltryptamine Chemical compound

α-Methyltryptamine is a psychedelic, stimulant, and entactogen drug of the tryptamine family. It was originally developed as an antidepressant at Upjohn in the 1960s, and was used briefly as an antidepressant in the Soviet Union under the brand name Indopan or Indopane before being discontinued.

<span class="mw-page-title-main">Empathogen</span> Class of psychoactive drugs that produce empathic experiences

Empathogens or entactogens are a class of psychoactive drugs that induce the production of experiences of emotional communion, oneness, relatedness, emotional openness—that is, empathy or sympathy—as particularly observed and reported for experiences with 3,4-methylenedioxymethamphetamine (MDMA). This class of drug is distinguished from the classes of hallucinogen or psychedelic, and amphetamine or stimulants. Major members of this class include MDMA, MDA, MDEA, MDOH, MBDB, 5-APB, 5-MAPB, 6-APB, 6-MAPB, methylone, mephedrone, GHB, αMT, and αET, MDAI among others. Most entactogens are phenethylamines and amphetamines, although several, such as αMT and αET, are tryptamines. When referring to MDMA and its counterparts, the term MDxx is often used. Entactogens are sometimes incorrectly referred to as hallucinogens or stimulants, although many entactogens such as ecstasy exhibit psychedelic or stimulant properties as well.

<span class="mw-page-title-main">3,4-Methylenedioxyamphetamine</span> Empathogen-entactogen, psychostimulant, and psychedelic drug of the amphetamine family

3,4-Methylenedioxyamphetamine (MDA), sometimes referred to as “sass,” is an empathogen-entactogen, stimulant, and psychedelic drug of the amphetamine family that is encountered mainly as a recreational drug. In its pharmacology, MDA is a serotonin–norepinephrine–dopamine releasing agent (SNDRA). In most countries, the drug is a controlled substance and its possession and sale are illegal.

<span class="mw-page-title-main">5-APDI</span> Chemical compound

5-(2-Aminopropyl)-2,3-dihydro-1H-indene (5-APDI), also known as indanylaminopropane (IAP), IAP (psychedelic), 2-API(2-aminopropylindane), indanametamine, and, incorrectly, as indanylamphetamine, is an entactogen and psychedelic drug of the amphetamine family. It has been sold by online vendors through the Internet and has been encountered as a designer drug since 2003, but its popularity and availability has diminished in recent years.

<span class="mw-page-title-main">Benzofuranylpropylaminopentane</span> Chemical compound

(–)-Benzofuranylpropylaminopentane is an experimental drug related to selegiline which acts as a monoaminergic activity enhancer (MAE). It is orally active in animals.

<span class="mw-page-title-main">5-Methyl-MDA</span> Chemical compound

5-Methyl-3,4-methylenedioxyamphetamine (5-Methyl-MDA) is an entactogen and psychedelic designer drug of the amphetamine class. It is a ring-methylated homologue of MDA and a structural isomer of MDMA.

<span class="mw-page-title-main">5-APDB</span> Chemical compound

5-(2-Aminopropyl)-2,3-dihydrobenzofuran is a putative entactogen drug of the phenethylamine and amphetamine classes. It is an analogue of MDA where the heterocyclic 3-position oxygen from the 3,4-methylenedioxy ring has been replaced by a methylene bridge. 6-APDB is an analogue of 5-APDB where the 4-position oxygen has been replaced by a methylene bridge instead. 5-APDB was developed by a team led by David E. Nichols at Purdue University as part of their research into non-neurotoxic analogues of MDMA.

<span class="mw-page-title-main">MDAI</span> Chemical compound

MDAI, also known as 5,6-methylenedioxy-2-aminoindane, is an entactogen drug of the 2-aminoindane group which is related to MDMA and produces similar subjective effects.

α-Methylserotonin Chemical compound

α-Methylserotonin (αMS), also known as α-methyl-5-hydroxytryptamine (α-methyl-5-HT) or 5-hydroxy-α-methyltryptamine (5-HO-αMT), is a tryptamine derivative closely related to the neurotransmitter serotonin (5-HT). It acts as a non-selective serotonin receptor agonist and has been used extensively in scientific research to study the function of the serotonin system.

<span class="mw-page-title-main">Monoamine releasing agent</span> Class of compounds

A monoamine releasing agent (MRA), or simply monoamine releaser, is a drug that induces the release of a monoamine neurotransmitter from the presynaptic neuron into the synapse, leading to an increase in the extracellular concentrations of the neurotransmitter. Many drugs induce their effects in the body and/or brain via the release of monoamine neurotransmitters, e.g., trace amines, many substituted amphetamines, and related compounds.

A serotonin releasing agent (SRA) is a type of drug that induces the release of serotonin into the neuronal synaptic cleft. A selective serotonin releasing agent (SSRA) is an SRA with less significant or no efficacy in producing neurotransmitter efflux at other types of monoamine neurons, including dopamine and norepinephrine neurons.

<span class="mw-page-title-main">5-IT</span> Chemical compound

5-(2-Aminopropyl)indole is an indole and phenethylamine derivative with empathogenic effects. Its preparation was first reported by Albert Hofmann in 1962. It is a designer drug that has been openly sold as a recreational drug by online vendors since 2011.

<span class="mw-page-title-main">Serotonin antagonist and reuptake inhibitor</span> Class of drug

Serotonin antagonist and reuptake inhibitors (SARIs) are a class of drugs used mainly as antidepressants, but also as anxiolytics and hypnotics. They act by antagonizing serotonin receptors such as 5-HT2A and inhibiting the reuptake of serotonin, norepinephrine, and/or dopamine. Additionally, most also antagonize α1-adrenergic receptors. The majority of the currently marketed SARIs belong to the phenylpiperazine class of compounds.

<span class="mw-page-title-main">6-APDB</span> Stimulant designer drug

6-(2-Aminopropyl)-2,3-dihydrobenzofuran is a stimulant and entactogen drug of the phenethylamine and amphetamine classes. It is an analogue of MDA where the heterocyclic 4-position oxygen from the 3,4-methylenedioxy ring has been replaced with a methylene bridge. 5-APDB (3-Desoxy-MDA) is an analogue of 6-APDB where the 3-position oxygen has been replaced with a methylene instead. 6-APDB, along with 5-APDB, was first synthesized by David E. Nichols in the early 1990s while investigating non-neurotoxic MDMA analogues.

<span class="mw-page-title-main">5-APB</span> Empathogenic psychoactive designer drug

5-APB is an empathogenic psychoactive compound of the substituted benzofuran, substituted amphetamine and substituted phenethylamine classes. 5-APB and other compounds are sometimes informally called "Benzofury".

A monoamine reuptake inhibitor (MRI) is a drug that acts as a reuptake inhibitor of one or more of the three major monoamine neurotransmitters serotonin, norepinephrine, and dopamine by blocking the action of one or more of the respective monoamine transporters (MATs), which include the serotonin transporter (SERT), norepinephrine transporter (NET), and dopamine transporter (DAT). This in turn results in an increase in the synaptic concentrations of one or more of these neurotransmitters and therefore an increase in monoaminergic neurotransmission.

<span class="mw-page-title-main">5-MAPB</span> Chemical compound

5-MAPB is an entactogenic designer drug similar to MDMA in its structure and effects.

<span class="mw-page-title-main">5-EAPB</span> Chemical compound

5-EAPB is a potentially entactogenic amphetamine which is structurally related to 5-MAPB and 5-APB. It might be predicted to show similar effects to these drugs in humans, but the pharmacology of 5-EAPB remains unstudied as of 2020.

<span class="mw-page-title-main">5-MAPDB</span> Chemical compound

5-MAPDB (1-(2,3-dihydrobenzofuran-5-yl)-N-methylpropan-2-amine) is a chemical compound which acts as an entactogenic drug. It is structurally related to drugs like 5-APDB and 5-MAPB, which have similar effects to MDMA and have been used as recreational drugs. 5-MAPDB has been studied to determine its pharmacological activity, and was found to be a relatively selective serotonin releaser, though with weaker actions as a releaser of other monoamines and 5-HT2 receptor family agonist, similar to older compounds such as 5-APDB.

<span class="mw-page-title-main">Substituted benzofuran</span> Class of chemical compounds

The substituted benzofurans are a class of chemical compounds based on the heterocyclyc and polycyclic compound benzofuran. Many medicines use the benzofuran core as a scaffold, but most commonly the term is used to refer to the simpler compounds in this class which include numerous psychoactive drugs, including stimulants, psychedelics and empathogens. In general, these compounds have a benzofuran core to which a 2-aminoethyl group is attached, and combined with a range of other substituents. Some psychoactive derivatives from this family have been sold under the name Benzofury.

References

  1. 1 2 3 4 5 6 Iversen 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. PMC   3582025 . PMID   23261499.
  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. PMC   4500375 . PMID   25765500.
  3. 1 2 Canal 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. PMC   5445387 . PMID   27903793.
  4. 1 2 USpatent 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. 1 2 3 Browne 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. ISBN   978-0-12-415816-0.
  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. PMID   26530501.
  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. PMC   3770991 . PMID   23733714.
  9. ↑ "Results". PRO Test. Retrieved 2021-06-01.
  10. 1 2 Casale 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 from the original (PDF) on 2016-11-05. Retrieved 2016-06-08.
  11. ↑ "Controlled Drugs and Substances Act : Definitions and Interpretations". isomerdesign.com. Retrieved 2019-11-11.
  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 . ISSN   2050-3245. S2CID   159675835.
  13. ↑ "21 CFR — SCHEDULES OF CONTROLLED SUBSTANCES §1308.11 Schedule I." Archived from the original on 2009-08-27. Retrieved 2018-04-10.
  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 from the original (PDF) on 2016-02-06. Retrieved 2016-05-31.
  18. ↑ "Loi du 19 février 1973 concernant la vente de substances médicamenteuses et la lutte contre la toxicomanie. - Legilux". legilux.public.lu. Retrieved 2021-06-01.
  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 from the original on 4 October 2013. Retrieved 15 September 2013.
  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). "关于将溴啡等46种物质列入《非药用类麻醉药品和精神药品管制品种增补目录》的公告".
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