6-APB: Difference between revisions

6-APB was first synthesized in 1993 by [[David E. Nichols]] as a potential non-neurotoxic alternative to [[MDMA]].<ref name="Nichols">Monte, A. P., Marona-Lewicka, D., Cozzi, N. V., & Nichols, D. E. (1993). Synthesis and pharmacological examination of benzofuran, indan, and tetralin analogs of 3, 4-(methylenedioxy) amphetamine. Journal of Medicinal Chemistry, 36(23), 3700-3706. https://doi.org/10.1021/jm00075a027</ref> However, it did not come into popular recreational use until over a decade later, where it briefly entered the rave scene and global research chemicals market. It was sold along with other novel benzofuran entactogens under the name "Benzofury" before its sale and import were subsequently banned.{{citation needed}}  

On June 10, 2013 6-APB and a number of analogues were classified as Temporary Class Drugs in the UK following an ACMD recommendation.<ref>Advisory Council on the Misuse of Drugs, Jeremy Browne (4 June 2013). "Temporary class drug order on benzofury and NBOMe compounds - letter from ACMD". GOV.UK.</ref> 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.<ref>UK Home Office (28 April 2014). "The Misuse of Drugs Act 1971 (Ketamine etc.) (Amendment) Order 2014". The National Archives.</ref>

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.<ref name="6APBpharm1">Iversen L, Gibbons S, Treble R, Setola V, Huang XP, Roth BL (2013). "Neurochemical profiles of some novel psychoactive substances". Eur. J. Pharmacol. 700 (1-3): 147–51. PMID 23261499. https://doi.org10.1016/j.ejphar.2012.12.006</ref> 6-APB also possesses additional activity as a [[releasing agent]] of these [[monoamine neurotransmitters]].<ref>Rickli A, Kopf S, Hoener MC, Liechti ME (2015). "Pharmacological profile of novel psychoactive benzofurans". Br. J. Pharmacol. 172 (13): 3412–25. PMID 25765500. https://doi.org/10.1111/bph.13128</ref>

6-APB is a potent [[Agonists#Types of agonist|full agonist]] of the serotonin 5-HT_2B receptor (Ki = 3.7 nM)<ref name="6APBpharm1" />, with higher affinity for this target than any other site.<ref name="5HT2C">Canal CE, Murnane KS (2017). "The serotonin 5-HT2C receptor and the non-addictive nature of classic hallucinogens". J. Psychopharmacol. (Oxford). 31 (1): 127–143. PMID 27903793. https://doi.org/10.1177/0269881116677104</ref> Moreover, unlike MDMA, 6-APB shows 100-fold selectivity for the 5-HT_2B receptor over the 5-HT_2A and 5-HT_2C receptors.<ref name="5HT2C" /><ref>US patent 7045545, Karin Briner, Joseph Paul Burkhart, Timothy Paul Burkholder, Matthew Joseph Fisher, William Harlan Gritton, Daniel Timothy Kohlman, Sidney Xi Liang, Shawn Christopher Miller, Jeffrey Thomas Mullaney, Yao-Chang Xu, Yanping Xu, "Aminoalkylbenzofurans as serotonin (5-HT(2c)) agonists", published 19 January 2000, issued 16 May 2006</ref>

The [[monoamine neurotransmitters]] known as [[serotonin]], [[dopamine]] and [[noradrenaline]] are the global [[neurotransmitters]] that modulate the brain's ability to feel pleasure, motivation, reward, planning, attention, and focus. When their reuptake is inhibited or their release is promoted, these neurotransmitters accumulate in the [[synaptic cleft]] (gaps between neurons) to non-ordinary levels, which makes them able to be reused. The result is neuronal activation at a multitude of brain regions which has the net result of producing a combination of stimulating, relaxing, disinhibiting and euphoric effects.<ref>New Insights into the Mechanism of Action of Amphetamines | http://www.annualreviews.org/doi/abs/10.1146/annurev.pharmtox.47.120505.105140</ref>

* [https://erowid.org/experiences/subs/exp_6APB.shtml Erowid Experience Vaults: 6-APB]

Due to only having a short history of human use, the toxicity and harm potential is not exactly known. Due to its similarity to MDMA, it is likely that the administration of repeated or high dosages of 6-APB may be both neurotoxic and cardiotoxic<ref>Drug-induced Valvulopathy: An Update | tpx.sagepub.com/content/38/6/837.full</ref><ref>Possible association between 3,4-methylenedioxymethamphetamine abuse and valvular heart disease. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/17950805</ref> in some form.

Short-term physical health risks of 6-APB consumption include [[dehydration]], [[insomnia]], and hyperthermia (overheating).<ref>Drug-induced hyperthermia | http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2044.1993.tb07423.x/abstract;jsessionid=FC30A9B157A2BAFC81048D8595714565.f02t03</ref> Continuous activity without sufficient rest or rehydration may cause body temperature to rise to dangerous levels, and loss of fluid via excessive sweating puts the body at further risk as the stimulating and euphoric properties of the substance may render the user oblivious to their energy expenditure for quite some time. Diuretics such as alcohol may exacerbate these risks further.

Although it has not been formally studied, small changes in ambient temperature may cause large changes in 6-APB-induced serotonergic neurotoxicity as is the case with [[MDMA]].<ref>(PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/9634574</ref><ref>Vasopressin and oxytocin secretion in response to the consumption of ecstasy in a clubbing population | http://jop.sagepub.com/content/20/3/400</ref>

As with MDMA, the long-term, heavy usage of 6-APB (i.e. regular daily or weekly usage) is likely cardiotoxic and may lead to valvulopathy (heart valve issues) via its significant affinity for the 5-HT_2B receptor.<ref>Drug-induced Valvulopathy: An Update | tpx.sagepub.com/content/38/6/837.full</ref><ref>Possible association between 3,4-methylenedioxymethamphetamine abuse and valvular heart disease. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/17950805</ref>

There is an increased risk of serotonin syndrome when 6-APB is taken with many antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs).{{citation needed}} Additionally, if 6-APB is taken with SSRIs and SNRIs, it is likely to be significantly less effective if it produces any discernible effects at all.

*'''Australia and New Zealand:''' 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.{{citation needed}}

*'''Canada:''' 6-APB is Schedule III in Canada as it is an analogue of MDA. The CDSA was updated as a result of the Safe Streets Act changing amphetamines from Schedule 3 to Schedule 1.{{citation needed}}

*'''Germany:''' 6-APB is controlled under Anlage II of the BtMG, making it illegal to manufacture, import, possess, sell, or transfer it without a license.<ref>{{cite web|url=http://archive.is/QEKft|accessdate=2018-01-12|title=Anlage II BtMG - Einzelnorm)}}</ref>

*'''Italy:''' 6-APB is illegal in Italy.<ref>http://www.salute.gov.it/imgs/C_17_pagineAree_3729_listaFile_itemName_0_file.pdf</ref>

*'''Sweden:''' 6-APB is prohibited in Sweden as a "health hazard" as of 2009.{{citation needed}}

*'''United Kingdom:''' On June 10, 2013, 6-APB and some analogues were classified as Temporary Class Drugs in the U.K. following an ACMD recommendation. On March 5, 2014, the U.K. 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.<ref>http://www.legislation.gov.uk/uksi/2014/1106/contents/made</ref>

*'''United States:''' 6-APB is unscheduled in the United States, but not currently approved by the Food and Drug Administration for human consumption.{{citation needed}}

*[[Designer drug]]

* Greene, S. L. (2013). Benzofurans and benzodifurans. In Novel Psychoactive Substances (pp. 383-392). https://doi.org/10.1016/B978-0-12-415816-0.00016-X