6-APB

Use and effects

6-APB is reported to produce entactogenic, stimulant, and mild psychedelic effects in humans.

Side effects

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

Interactions

Pharmacology

Pharmacodynamics

6-APB acts as a serotonin–norepinephrine–dopamine releasing agent (SNDRA), with values for monoamine release of 36nM for serotonin, 14nM for norepinephrine, and 10nM for dopamine in rat brain synaptosomes. Simultaneously, 6-APB is a serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI), with affinities (Ki) of 117nM for the norepinephrine transporter (NET), 150nM for the dopamine transporter (DAT), and 2,698nM for the serotonin transporter (SERT) as well as values for monoamine reuptake inhibition of 930nM for serotonin, 190nM for norepinephrine, and 3,300nM for dopamine.

In addition to actions at the monoamine transporters, 6-APB is a potent high-efficacy partial agonist or full agonist of the serotonin 5-HT2B receptor (Ki = 3.7nM; = 140nM; = 70%). It has higher affinity for this target than any other site. Moreover, unlike MDMA, 6-APB shows 100-fold selectivity for the serotonin 5-HT2B receptor over the serotonin 5-HT2A and 5-HT2C receptors in terms of affinity. It is notably both more potent and more selective as an agonist of the serotonin 5-HT2B receptor than the reference serotonin 5-HT2B receptor agonist, BW-723C86, which is commonly used for research into the serotonin 5-HT2B receptor. Although much more potent at the serotonin 5-HT2B receptor, 6-APB is also a partial agonist of the serotonin 5-HT2A receptor (EC50 = 5,900nM; Emax = 43%) and shows affinity for the serotonin 5-HT2C receptor (Ki = 270nM) and the serotonin 5-HT1A receptor (Ki = 1,500nM). 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.

Besides the serotonin 5-HT2 receptors, 6-APB has been found to bind with high affinity to the α2C-adrenergic receptor (Ki = 45nM), although the significance of this action in humans is unknown. 6-APB showed little other affinity at a wide selection of other sites, with some exceptions like the rodent trace amine-associated receptor 1 (TAAR1).

The potent agonism of the serotonin 5-HT2B receptor makes it likely that 6-APB would be cardiotoxic with chronic or long-term use, as seen with other serotonin 5-HT2B receptor agonists such as the withdrawn serotonergic anorectic fenfluramine.

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 to 120minutes. The drugs peak effects last 7hours, followed by a comedown phase of approximately 2hours, and after effects for up to 24hours.

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.

Chemistry

6-APB, also known as 6-(2-aminopropyl)benzofuran, is a phenethylamine, amphetamine, and benzofuran and an analogue of 3,4-methylenedioxyamphetamine (MDA).

Synthesis

The chemical synthesis of 6-APB has been described. The synthesis by Briner and colleagues 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.

Reagent results

6-APB and its structural isomer 5-APB have been tested with a series of agents including: Marquis, Liebermann, Mecke, and Froehde reagents. 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 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.

Analogues

Analogues of 6-APB include MDA, 6-APDB, 6-MAPB, 5-APB, 6-APBT, and 6-API, among others.

History

6-APB, along with 5-APB, was first described in the scientific literature by Karin Briner and colleagues at Eli Lilly and Company in a patent in 2000. They were specifically studied as serotonin 5-HT2C receptor agonists for potential medical applications at this time. The description of 5-APB and 6-APB in the literature had followed the earlier work on 5-APDB and 6-APDB as serotonin releasing agents and entactogens by David E. Nichols and colleagues at Purdue University in 1993. 6-APB, along with 5-APB, emerged as a novel designer drug in 2010. 5-APB and 6-APB are often confused with 5-APDB and 6-APDB.

Society and culture

Legal status

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.

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" 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.

China

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

Finland

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

France

6-APB is illegal in France.

Germany

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

Italy

6-APB is illegal in Italy.

Luxembourg

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

Netherlands

6-APB, as well as multiple substances based on the phenylethamine structure, like most cathinones and amphetamines, are banned under the Opium Law since July 1st, 2025, following an amendment to deal with New Psychoactive Substances (NPS) in the Netherlands. 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.

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.

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).

It is also classified as a narcotic substance since 2020.

United Kingdom

On June 10, 2013 6-APB and a number of analogues were classified as Temporary Class Drugs in the UK following an ACMD recommendation. This means that sale and import of the named substances are criminal offences and are treated as for class B drugs. On November 28, 2013 the ACMD recommended that 6-APB and related benzofurans should become Class B, Schedule 1 substances. 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.

United States

6-APB is not an explicitly controlled substance in the United States. However, it could be considered a controlled substance under the Federal Analogue Act if intended for human consumption.

References

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