:Substituted cathinone

The following is a list of serotonin, dopamine, and norepinephrine releasing profiles for various cathinones, measured in rat brain synaptosomes.

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The derivatives may be produced by substitutions at four locations of the cathinone molecule:

• R₁ = hydrogen, or any combination of one or more alkyl, alkoxy, alkylenedioxy, haloalkyl or halide substituents
• R₂ = hydrogen or any alkyl group
• R₃ = hydrogen, any alkyl group, or incorporation in a cyclic structure
• R₄ = hydrogen, any alkyl group, or incorporation in a cyclic structure

The following table displays notable derivatives that have been reported:[http://www.emcdda.europa.eu/system/files/publications/550/2008_Implementation_report_281411.pdf Europol 2008 Annual Report on the implementation of Council Decision 2005/387/JHA][http://www.emcdda.europa.eu/system/files/publications/553/2009_Implementation_report_281420.pdf Europol 2009 Annual Report on the implementation of Council Decision 2005/387/JHA][http://www.emcdda.europa.eu/system/files/publications/644/EMCDDA-Europol_Annual_Report_2010A_281336.pdf Europol 2010 Annual Report on the implementation of Council Decision 2005/387/JHA][http://www.emcdda.europa.eu/system/files/publications/689/EMCDDA-Europol_Annual_Report_2011_2012_final_335568.pdf Europol 2011 Annual Report on the implementation of Council Decision 2005/387/JHA][http://www.emcdda.europa.eu/system/files/publications/734/EMCDDA-Europol_2012_Annual_Report_final_439477.pdf Europol 2012 Annual Report on the implementation of Council Decision 2005/387/JHA][http://www.emcdda.europa.eu/system/files/publications/814/TDAN14001ENN_475519.pdf Europol 2013 Annual Report on the implementation of Council Decision 2005/387/JHA][http://www.emcdda.europa.eu/system/files/publications/1018/TDAN15001ENN.pdf Europol 2014 Annual Report on the implementation of Council Decision 2005/387/JHA][http://www.emcdda.europa.eu/system/files/publications/2880/TDAS16001ENN.pdf Europol 2015 Annual Report on the implementation of Council Decision 2005/387/JHA][http://www.emcdda.europa.eu/system/files/publications/4724/TDAN17001ENN_PDFWEB.pdf Europol 2016 Annual Report on the implementation of Council Decision 2005/387/JHA][http://www.emcdda.europa.eu/system/files/publications/9282/20183924_TDAN18001ENN_PDF.pdf Europol 2017 Annual Report on the implementation of Council Decision 2005/387/JHA]{{cite book | url = https://www.emcdda.europa.eu/system/files/publications/13464/20205648_TD0320796ENN_PDF_rev.pdf | title = New psychoactive substances: global markets, glocal threats and the COVID-19 pandemic. An update from the EU Early Warning System | author = European Monitoring Center for Drugs and Drug Addiction | location = Luxembourg | publisher = Publications Office of the European Union | date = December 2020 | doi = 10.2810/921262 | isbn = 9789294975584 }}{{cite journal | vauthors = Maurer HH, Kraemer T, Springer D, Staack RF | title = Chemistry, pharmacology, toxicology, and hepatic metabolism of designer drugs of the amphetamine (ecstasy), piperazine, and pyrrolidinophenone types: a synopsis | journal = Therapeutic Drug Monitoring | volume = 26 | issue = 2 | pages = 127–31 | date = April 2004 | pmid = 15228152 | doi = 10.1097/00007691-200404000-00007 | s2cid = 9255084 }}{{cite journal | vauthors = Davis S, Rands-Trevor K, Boyd S, Edirisinghe M | title = The characterisation of two halogenated cathinone analogues: 3,5-difluoromethcathinone and 3,5-dichloromethcathinone | journal = Forensic Science International | volume = 217 | issue = 1–3 | pages = 139–45 | date = April 2012 | pmid = 22088945 | doi = 10.1016/j.forsciint.2011.10.042 }}{{cite journal | vauthors = Liu C, Jia W, Li T, Hua Z, Qian Z | title = Identification and analytical characterization of nine synthetic cathinone derivatives N-ethylhexedrone, 4-Cl-pentedrone, 4-Cl-α-EAPP, propylone, N-ethylnorpentylone, 6-MeO-bk-MDMA, α-PiHP, 4-Cl-α-PHP, and 4-F-α-PHP | journal = Drug Testing and Analysis | volume = 9 | issue = 8 | pages = 1162–1171 | date = August 2017 | pmid = 27863142 | doi = 10.1002/dta.2136 }}{{cite journal | vauthors = Błażewicz A, Bednarek E, Popławska M, Olech N, Sitkowski J, Kozerski L | title = Identification and structural characterization of synthetic cathinones: N-propylcathinone, 2,4-dimethylmethcathinone, 2,4-dimethylethcathinone, 2,4-dimethyl-α-pyrrolidinopropiophenone, 4-bromo-α-pyrrolidinopropiophenone, 1-(2,3-dihydro-1H-inden-5-yl)-2-(pyrrolidin-1-yl)hexan-1-one and 2,4-dimethylisocathinone. | journal = Forensic Toxicol | date = 2019 | volume = 37 | issue = 2 | pages = 288–307 | doi = 10.1007/s11419-018-00463-w | s2cid = 59618061 | doi-access = free }}{{cite journal | vauthors = Westphal F, Girreser U, Angerer V, Auwärter V | title = Analytische Daten neuer 2-aminosubstituierter Methylendioxyvalerophenonderivate. | journal = Toxichem Krimtech | date = January 2016 | volume = 83 | issue = 1 | pages = 3–29 }}{{cite journal | vauthors = Majchrzak M, Celiński R, Kuś P, Kowalska T, Sajewicz M | title = The newest cathinone derivatives as designer drugs: an analytical and toxicological review | journal = Forensic Toxicology | volume = 36 | issue = 1 | pages = 33–50 | date = 2018 | pmid = 29367861 | pmc = 5754390 | doi = 10.1007/s11419-017-0385-6 }}{{cite journal | vauthors = Carlsson A, Sandgren V, Svensson S, Konradsson P, Dunne S, Josefsson M, Dahlén J | title = Prediction of designer drugs: Synthesis and spectroscopic analysis of synthetic cathinone analogs that may appear on the Swedish drug market | journal = Drug Testing and Analysis | volume = 10| issue = 7| date = February 2018 | pages = 1076–1098 | pmid = 29426062 | doi = 10.1002/dta.2366 }}{{cite journal | vauthors = Cheng WC, Wong WC | title = Forensic drug analysis of chloro-N,N-dimethylcathinone (CDC) and chloroethcathinone (CEC): Identification of 4-CDC and 4-CEC in drug seizures and differentiation from their ring-substituted positional isomers | journal = Forensic Science International | volume = 298 | pages = 268–277 | date = May 2019 | pmid = 30925345 | doi = 10.1016/j.forsciint.2019.03.002 | s2cid = 87589412 }}{{cite journal | vauthors = Lajtai A, Mayer M, Lakatos Á, Kuzma M, Miseta A | title = New psychoactive versus conventional stimulants - a ten-year review of casework in Hungary | journal = Legal Medicine | volume = 47 | pages = 101780 | date = November 2020 | pmid = 32882537 | doi = 10.1016/j.legalmed.2020.101780 | s2cid = 221496728 | doi-access = free }}{{cite journal | vauthors = Jones NS, Comparin JH | title = Interpol review of controlled substances 2016-2019 | journal = Forensic Science International. Synergy | volume = 2 | pages = 608–669 | date = 2020 | pmid = 33385148 | pmc = 7770462 | doi = 10.1016/j.fsisyn.2020.01.019 }}{{cite web | url = https://finlex.fi/fi/lainsaadanto/2014/1130 | title = Valtioneuvoston asetus kuluttajamarkkinoilta kielletyistä psykoaktiivisista aineista | trans-title = Government Decree on Psychoactive Substances Banned from the Consumer Market | language = Finnish | work = Finlex Data Bank }}

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On 2 April 2010, the Advisory Council on the Misuse of Drugs in the UK announced that a broad structure-based ban of this entire class of compounds would be instituted, following extensive publicity around grey-market sales and recreational use of mephedrone, a common member of the family. This ban covers compounds with the aforementioned general structure, with 28 compounds specifically named.Advisory Council on the Misuse of Drugs (UK). [http://www.homeoffice.gov.uk/publications/alcohol-drugs/drugs/acmd1/acmd-cathinodes-report-2010?view=Binary Consideration of the cathinones. 31 March 2010.] {{Webarchive|url=https://web.archive.org/web/20110922230621/http://www.homeoffice.gov.uk/publications/alcohol-drugs/drugs/acmd1/acmd-cathinodes-report-2010?view=Binary |date=22 September 2011 }} Retrieved 2011-07-17.

{{blockquote|"Any compound (not being bupropion or a substance for the time being specified in paragraph 2.2) structurally derived from 2-amino-1-phenyl-1-propanone by modification in any of the following ways, that is to say,

(i) by substitution in the phenyl ring to any extent with alkyl, alkoxy, alkylenedioxy, haloalkyl or halide substituents, whether or not further substituted in the phenyl ring by one or more other univalent substituents;

(ii) by substitution at the 3-position with an alkyl substituent;

(iii) by substitution at the nitrogen atom with alkyl or dialkyl groups, or by inclusion of the nitrogen atom in a cyclic structure."|ACMD, 2 April 2010}}

This text was added as an amendment to the Misuse of Drugs Act 1971, to come into force on 16 April 2010.{{cite web|url=http://www.opsi.gov.uk/si/si2010/uksi_20101144_en_1 |title=The Misuse of Drugs (Amendment) (England, Wales and Scotland) Regulations 2010 No. 1144 |publisher=Opsi.gov.uk |access-date=2010-04-08}} Note that four of the above compounds (cathinone, methcathinone, diethylpropion and pyrovalerone) were already illegal in the UK at the time the ACMD report was issued. Two compounds were specifically excluded from the ban, these being bupropion because of its common use in medicine and relative lack of abuse potential, and naphyrone because its structure falls outside the generic definition and not enough evidence was yet available to justify a ban.

Naphyrone analogues were subsequently banned in July 2010 following a further review by the ACMD,{{cite web|url=http://news.bbc.co.uk/1/hi/uk/10602398.stm |title=NRG-1 'legal high' drug is banned |publisher=BBC News |date=2010-07-12 |access-date=2010-07-17}}{{cite web|url=http://www.homeoffice.gov.uk/publications/drugs/acmd1/naphyrone-report |title=Advisory Council on the Misuse of Drugs Naphyrone Report (2010) |publisher=Home Office |date=2010-07-07 |access-date=2010-07-17 |url-status=dead |archive-url=https://web.archive.org/web/20100717121420/http://www.homeoffice.gov.uk/publications/drugs/acmd1/naphyrone-report |archive-date=17 July 2010 }} along with a further broad based structure ban even more expansive than the last.{{cite web|url=http://www.opsi.gov.uk/si/si2010/em/uksiem_20101799_en.pdf |title=Explanatory Memorandum To The Misuse of Drugs (Amendment No. 2) (England, Wales and Scotland) Regulations 2010 No. 1799 |publisher=Opsi.gov.uk |access-date=2010-07-18}}{{cite web|url=http://www.opsi.gov.uk/si/si2010/pdf/uksi_20101799_en.pdf |title=The Misuse of Drugs (Amendment No. 2) (England, Wales and Scotland) Regulations 2010 No. 1799 |publisher=Opsi.gov.uk |access-date=2010-07-18}}

{{blockquote|"Any compound structurally derived from 2–aminopropan–1–one by substitution at the 1-position with any monocyclic, or fused-polycyclic ring system (not being a phenyl ring or alkylenedioxyphenyl ring system), whether or not the compound is

further modified in any of the following ways, that is to say—

(i) by substitution in the ring system to any extent with alkyl, alkoxy, haloalkyl

or halide substituents, whether or not further substituted in the ring system by

one or more other univalent substituents;

(ii) by substitution at the 3–position with an alkyl substituent;

(iii) by substitution at the 2-amino nitrogen atom with alkyl or dialkyl groups, or

by inclusion of the 2-amino nitrogen atom in a cyclic structure".|Home Office, 13 July 2010.}}

File:Naphyrone general.pngThe substitutions in the general structure for naphyrone analogues subject to the ban may be described as follows:

• Cyc = any monocyclic, or fused-polycyclic ring system (not being a phenyl ring or alkylenedioxyphenyl ring system), including analogues where the ring system is substituted to any extent with alkyl, alkoxy, haloalkyl or halide substituents, whether or not further substituted in the ring system by one or more other univalent substituents
• R₁ = hydrogen or any alkyl group
• R₂ = hydrogen, any alkyl group, or incorporation in a cyclic structure
• R₃ = hydrogen, any alkyl group, or incorporation in a cyclic structure

More new derivatives have however continued to appear, with the UK reporting more novel cathinone derivatives detected in 2010 than any other country in Europe, with most of them first identified after the generic ban had gone into effect and thus already being illegal despite never having been previously reported.European Monitoring Centre on Drugs and Drug Addiction. [http://www.emcdda.europa.eu/attachements.cfm/att_132857_EN_EMCDDA-Europol%20Annual%20Report%202010A.pdf EMCDDA–Europol 2010 Annual Report on the implementation of Council Decision 2005/387/JHA.] {{Webarchive|url=https://web.archive.org/web/20120314043454/http://www.emcdda.europa.eu/attachements.cfm/att_132857_EN_EMCDDA-Europol%20Annual%20Report%202010A.pdf |date=14 March 2012 }} Retrieved 2011-07-17.

In the United States, substituted cathinones are the psychoactive ingredients in "bath salts" which as of July 2011 were banned by at least 28 states, but not by the federal government.{{cite web | vauthors = Goodnough A, Zezima K | url = https://www.nytimes.com/2011/07/17/us/17salts.html | title = An Alarming New Stimulant, Legal in Many States. | work = The New York Times | date = 16 July 2011 | access-date = 17 July 2011 }}

• Markush structure
• Substituted amphetamines
• Substituted β-hydroxyamphetamines
• Substituted methylenedioxyphenethylamines
• Substituted phenethylamines
• Substituted phenylmorpholines
• Substituted β-ketotryptamines
• Structural scheduling of synthetic cannabinoids
• Arylcyclohexylamines
• List of aminorex analogues
• List of fentanyl analogues
• List of methylphenidate analogues

{{Reflist}}

• {{Cite web | url = https://www.euda.europa.eu/publications/drug-profiles/synthetic-cathinones_en | publisher = European Union Drugs Agency (EUDA) | title = Synthetic cathinones}}

{{Phenethylamines}}

{{Chemical classes of psychoactive drugs}}

{{Monoamine releasing agents}}

{{Monoamine reuptake inhibitors}}

Category:Chemical classes of psychoactive drugs