Editing Cathinone

{{Short description|Chemical compound}}
{{about|the specific chemical compound cathinone|the class of similar substances|substituted cathinone}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox drug
| Verifiedfields     = changed
| Watchedfields      = changed
| verifiedrevid      = 447622611
| IUPAC_name         = ''(S)''-2-Amino-1-phenylpropan-1-one
| image              = Cathinone.svg
| width              = 140
| image2             = Cathinone molecule ball.png

<!--Clinical data-->
| tradename          = 
| pregnancy_category = 
| legal_AU           = S9
| legal_BR           = F2
| legal_BR_comment   = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-07-24 |title=RDC Nº 804 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 804 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-804-de-24-de-julho-de-2023-498447451 |url-status=live |archive-url=https://web.archive.org/web/20230827163149/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-804-de-24-de-julho-de-2023-498447451 |archive-date=2023-08-27 |access-date=2023-08-27 |publisher=[[Diário Oficial da União]] |language=pt-BR |publication-date=2023-07-25}}</ref>
| legal_CA           = Schedule III
| legal_DE           = Anlage I
| legal_UK           = Class c
| legal_US           = Schedule I
| legal_UN           = P I

<!--Pharmacokinetic data-->
| dependency_liability = [[Physical dependence|Physical]]: no data
[[Psychological dependence|Psychological]]: Low–moderate<ref>Nutt D, King LA, Blakemore C (March 2007). "Development of a rational scale to assess the harm of drugs of potential misuse". Lancet. 369 (9566): 1047–53. doi:10.1016/S0140-6736(07)60464-4. PMID 17382831. S2CID 5903121.</ref>
| addiction_liability = 
| metabolism         = 
| elimination_half-life = 0.7–2.3 h<ref>{{cite journal | vauthors = Toennes SW, Harder S, Schramm M, Niess C, Kauert GF | title = Pharmacokinetics of cathinone, cathine and norephedrine after the chewing of khat leaves | journal = British Journal of Clinical Pharmacology | volume = 56 | issue = 1 | pages = 125–130 | date = July 2003 | pmid = 12848785 | pmc = 1884326 | doi = 10.1046/j.1365-2125.2003.01834.x }}</ref>
| excretion          =

<!--Identifiers-->
| CAS_number_Ref     = {{cascite|correct|??}}
| CAS_number         = 71031-15-7
| ATC_prefix         = none
| PubChem            = 62258
| DrugBank_Ref       = {{drugbankcite|correct|drugbank}}
| DrugBank           = DB01560
| ChemSpiderID_Ref   = {{chemspidercite|correct|chemspider}}
| ChemSpiderID       = 56062
| ChEMBL_Ref         = {{ebicite|changed|EBI}}
| ChEMBL             = 2104047
| UNII_Ref           = {{fdacite|correct|FDA}}
| UNII               = 540EI4406J
| KEGG_Ref           = {{keggcite|correct|kegg}}
| KEGG               = C08301
| ChEBI_Ref          = {{ebicite|correct|EBI}}
| ChEBI              = 4110
| synonyms           = β-Ketoamphetamine; Benzoylethanamine<ref>{{cite journal | vauthors = Hosseinian A, Vessally E, Bekhradnia A, Nejati K, Rahimpour G |title=Benzoylethanamine drug interaction with the AlN nanosheet, nanotube and nanocage: Density functional theory studies |journal=Thin Solid Films |date=31 October 2017 |volume=640 |pages=93–98 |doi=10.1016/j.tsf.2017.08.049}}</ref>

<!--Chemical data-->
| C                  = 9
| H                  = 11
| N                  = 1
| O                  = 1
| SMILES             = O=C(c1ccccc1)[C@@H](N)C
| StdInChI_Ref       = {{stdinchicite|correct|chemspider}}
| StdInChI           = 1S/C9H11NO/c1-7(10)9(11)8-5-3-2-4-6-8/h2-7H,10H2,1H3/t7-/m0/s1
| StdInChIKey_Ref    = {{stdinchicite|correct|chemspider}}
| StdInChIKey        = PUAQLLVFLMYYJJ-ZETCQYMHSA-N
}}

'''Cathinone''' ({{IPAc-en|ˈ|k|æ|θ|ᵻ|n|oʊ|n}}; also known as '''β-ketoamphetamine''') is a [[monoamine]] [[alkaloid]] found in the [[shrub]] ''[[Catha edulis]]'' (khat) and is chemically similar to [[ephedrine]], [[cathine]], [[methcathinone]] and other [[amphetamines]]. It is probably the main contributor to the [[stimulant]] effect of ''Catha edulis''. Cathinone differs from many other amphetamines in that it has a [[ketone]] [[functional group]]. Other phenethylamines that share this structure include the stimulants [[methcathinone]], [[MDPV]], [[mephedrone]] and the [[antidepressant]] [[bupropion]].

==History==
===Discovery===
[[Khat]] has been cultivated in the [[Horn of Africa]] and [[Arabian Peninsula]] region of the world for thousands of years. It is most commonly chewed for the [[euphoria|euphoric]] effect it produces. The active ingredient was first proposed in 1930, when [[cathine]] was identified as a predominant alkaloid in the plant.<ref name="Patel">{{cite journal | vauthors = Patel NB | title = Mechanism of action of cathinone: the active ingredient of khat (Catha edulis) | journal = East African Medical Journal | volume = 77 | issue = 6 | pages = 329–332 | date = June 2000 | pmid = 12858935 | doi = 10.4314/eamj.v77i6.46651 | doi-access = free }}</ref> Cathine was thought to be the main active ingredient in khat until the 1960s, when it was found that the amount of cathine in the khat leaves is insufficient to produce the effects observed. In 1975, the United Nations Narcotic Laboratory analyzed khat leaves from [[Yemen]], [[Kenya]] and [[Madagascar]] and found evidence of a different alkaloid, cathinone.<ref name="Patel"/> Cathinone is molecularly similar to cathine, but is much more abundant in younger plants.  This finding caused scientists to speculate that cathinone was the true active ingredient in khat.<ref name="Patel"/>

A study was conducted in 1994 to test the effects of cathinone. Six volunteers who had never chewed khat were given an active khat sample and a cathinone-free [[placebo]] sample.<ref name="Wilder">{{cite journal | vauthors = Widler P, Mathys K, Brenneisen R, Kalix P, Fisch HU | title = Pharmacodynamics and pharmacokinetics of khat: a controlled study | journal = Clinical Pharmacology and Therapeutics | volume = 55 | issue = 5 | pages = 556–562 | date = May 1994 | pmid = 7910126 | doi = 10.1038/clpt.1994.69 | s2cid = 25788465 }}</ref> The researchers analyzed the participants' moods, activity levels and blood pressure before and after consuming the khat or placebo. This analysis showed that cathinone produced amphetamine-like effects, leading the researchers to confirm that cathinone, not cathine, is the active ingredient in khat leaves.<ref name="Wilder"/>

===Cultural significance===
[[File:Qat man.jpg|thumb|left|Man chewing khat]]
Over 20 million people in the [[Arabian Peninsula]] and [[East Africa]] chew khat leaves daily.  It is an important piece of the culture and economy in this region, especially in [[Ethiopia]] (where khat is said to have originated), Kenya, [[Djibouti]], Somalia and Yemen.  Men usually chew it during parties or other social gatherings while smoking cigarettes and drinking tea.  Farmers and other workers also use khat in the afternoon to reduce fatigue and hunger as the day goes on.  It functions like the [[caffeine]] in a strong cup of coffee as an anti-fatigue drug.  Students and drivers have been known to use it to stay alert for longer periods of time.<ref name="Kirby">{{cite news| vauthors = Kirby A |title=Yemen's khat habit soaks up water |url=http://news.bbc.co.uk/2/hi/programmes/from_our_own_correspondent/6530453.stm |website=BBC News|date=7 April 2007|publisher=BBC|access-date=20 March 2015|url-status=live|archive-url= https://web.archive.org/web/20141012084142/http://news.bbc.co.uk/2/hi/programmes/from_our_own_correspondent/6530453.stm|archive-date=12 October 2014}}</ref>

In order to produce its desired effects, khat leaves should be chewed fresh.  The fresh leaves have a higher concentration of cathinone.  Waiting too long after cultivation to chew the leaf will allow the cathinone to break down into its less potent form, cathine.  Because of the need for quick chewing, it is a habit that has historically been prevalent only where the plant grows.  However, in the recent years with improvements in road and air transport, khat chewing has spread to all corners of the world.

The cultivation of khat in Yemen is a highly profitable industry for farmers.  Khat plants will grow differently depending on the climate they are grown in and each one will produce different amounts of cathinone.<ref name="Al-Motarreb">{{cite journal | vauthors = Al-Motarreb A, Baker K, Broadley KJ | title = Khat: pharmacological and medical aspects and its social use in Yemen | journal = Phytotherapy Research | volume = 16 | issue = 5 | pages = 403–413 | date = August 2002 | pmid = 12203257 | doi = 10.1002/ptr.1106 | s2cid = 9749292 }}</ref>  It generally grows best in coastal, hot climates.  In Yemen, the khat plant is named after the region in which it is grown.  The Nehmi khat plant has the highest known concentration of cathinone, 342.5&nbsp;mg/100&nbsp;g.<ref name="Al-Motarreb"/>

===Legality===
Internationally, cathinone is a [[Convention on Psychotropic Substances#Schedules of Controlled Substances|Schedule I]] drug under the [[Convention on Psychotropic Substances]].<ref name="urlwww.incb.org">{{cite web | url = http://www.incb.org/pdf/e/list/green.pdf | archive-url = https://web.archive.org/web/20120831222336/http://www.incb.org/pdf/e/list/green.pdf | archive-date = 2012-08-31 | title = List of psychotropic substances under international control | work = International Narcotics Control Board | publisher = United Nations | year = 2003 }}</ref> Circa 1993, the [[Drug Enforcement Administration|DEA]] added cathinone to the [[Controlled Substances Act]]'s Schedule I.

The sale of khat is legal in some jurisdictions, but illegal in others (see [[Khat#Regulation|Khat (Regulation)]]). [[Substituted cathinone]]s were also often used as the key ingredient of recreational drug mixes commonly known as "[[Bath salts (drug)|bath salts]]" in the United States.<ref>{{cite news |url=https://www.pbs.org/newshour/bb/science/july-dec12/bathsalts_09-20.html | archive-url = https://web.archive.org/web/20121229055853/https://www.pbs.org/newshour/bb/science/july-dec12/bathsalts_09-20.html | archive-date = 29 December 2012 |title=Synthetic Street Drug Camouflaged as Bath Salts Has Dangerous, Bizarre Effects |publisher=PBS NewsHour |date=20 September 2012 |access-date=7 December 2013 |url-status=dead }}</ref><ref>{{cite web| vauthors = Urquhart C | date =  4 September 2004 | work = The Guardian | url = https://www.theguardian.com/world/2004/sep/04/Israel | title = Drugs and dance as Israelis blot out intifada | archive-url = https://web.archive.org/web/20161108053442/https://www.theguardian.com/world/2004/sep/04/israel | archive-date = 8 November 2016 | access-date = 19 April 2015 }}</ref><ref>{{cite web | vauthors = Chai C | date = 16 April 2015 | work = Globalnews.ca | url = http://globalnews.ca/news/1942263/what-you-need-to-know-about-flakka-the-latest-drug-causing-erratic-behaviour/ | title = What you need to know about flakka, the latest drug causing erratic behaviour | archive-url = https://web.archive.org/web/20150420001955/http://globalnews.ca/news/1942263/what-you-need-to-know-about-flakka-the-latest-drug-causing-erratic-behaviour/ | archive-date = 20 April 2015 | access-date = 19 April 2015 }}</ref><ref name="Chemistry World">{{cite web |vauthors=Extance A |title=The rising tide of 'legal highs' |url=https://www.chemistryworld.com/feature/the-rising-tide-of-legal-highs/3007738.article |website=Chemistry World |access-date=3 August 2018 |language=en |archive-date=3 August 2018 |archive-url=https://web.archive.org/web/20180803224149/https://www.chemistryworld.com/feature/the-rising-tide-of-legal-highs/3007738.article |url-status=live }}</ref>

The table below shows the legality of khat and cathinone in various countries:
{| class="wikitable"
|-http://www.who.int/countries/eri/en/
! Region !! Regulation
|-
| Eritrea || Legal
|-
| Ethiopia || Legal
|-
| Somalia || Legal
|-
| Djibouti || Legal
|-
| Kenya || Khat is legal but cathinone and cathine are classified as Class C substances
|-
| South Africa || Khat is a protected plant
|-
| China || Illegal
|-
| Israel || Legal – The khat plant leaves are allowed to be chewed and beverages containing khat are legal, but it is illegal to sell pills based on cathinone extracts
|-
| Malaysia || Illegal
|-
| Saudi Arabia || Illegal
|-
| Yemen || Khat is legal but the cultivation and selling of the plant is regulated by the government
|-
| Denmark || Illegal
|-
| Finland || Illegal
|-
| France || Khat is prohibited as a stimulant
|-
| Germany || Khat is illegal but a derivative of cathinone is available upon prescription
|-
| Ireland || Illegal unless authorized
|-
| Netherlands || Cathinone and cathine have been illegal but khat was announced as illegal in 2012
|-
| Norway || Illegal
|-
| Poland || Illegal
|-
| Sweden || Illegal
|-
| Switzerland || Illegal
|-
| United Kingdom || Illegal
|-
| Canada || Illegal to obtain unless approved by a medical practitioner
|-
| United States || Illegal
|-
| Australia || Illegal
|-
| New Zealand || Illegal
|-
| Georgia || The khat plant itself is allowed to be sold and chewed, but it is illegal to sell or make beverages containing khat
|-
| Turkey || Illegal <ref>{{Cite web|url=https://www.resmigazete.gov.tr/eskiler/2011/02/20110213-4.htm|title=Başbakanlık Mevzuatı Geliştirme ve Yayın Genel Müdürlüğü|website=www.resmigazete.gov.tr}}</ref>
|-
| Bulgaria || Illegal under List I - "Plants and substances with a high risk to the public health due to their harmful effect of misuse, prohibited for use in human and veterinary medicine"<ref>{{cite web |url=http://www.mh.government.bg/media/filer_public/2015/06/19/naredba-red-za-klasifitsirane-na-rasteniyata-i-veshtestvata-kato-narkotichni-08-11-2013.pdf | title = НАРЕДБА за реда за класифициране на растенията и веществата като наркотични | language = Bulgarian | trans-title=REGULATION on the procedure for classifying plants and substances as narcotic | work = Ministry of Health | publisher = Republic of Bulgaria |access-date=2017-08-26 |url-status=live |archive-url=https://web.archive.org/web/20170827003245/http://www.mh.government.bg/media/filer_public/2015/06/19/naredba-red-za-klasifitsirane-na-rasteniyata-i-veshtestvata-kato-narkotichni-08-11-2013.pdf |archive-date=2017-08-27 }}</ref>
|}

==Pharmacology==

===Pharmacodynamics===
{| class="wikitable floatright" style="font-size:small;"
|+ {{Nowrap|[[Monoamine releasing agent|Monoamine release]] of cathinone and related agents ({{Abbrlink|EC<sub>50</sub>|Half maximal effective concentration}}, nM)}}
|-
! Compound !! data-sort-type="number" | {{abbrlink|NE|Norepinephrine}} !! data-sort-type="number" | {{abbrlink|DA|Dopamine}} !! data-sort-type="number" | {{abbrlink|5-HT|Serotonin}} !! Ref
|-
| [[Phenethylamine]] || 10.9 || 39.5 || >10,000 || <ref name="ReithBLoughHong2015">{{cite journal | vauthors = Reith ME, Blough BE, Hong WC, Jones KT, Schmitt KC, Baumann MH, Partilla JS, Rothman RB, Katz JL | title = Behavioral, biological, and chemical perspectives on atypical agents targeting the dopamine transporter | journal = Drug and Alcohol Dependence | volume = 147 | issue =  | pages = 1–19 | date = February 2015 | pmid = 25548026 | pmc = 4297708 | doi = 10.1016/j.drugalcdep.2014.12.005 }}</ref><ref name="Forsyth2012" /><ref name="Blough2008" />
|-
| [[Amphetamine]] || {{Abbr|ND|No data}} || {{Abbr|ND|No data}} || {{Abbr|ND|No data}} || {{Abbr|ND|No data}}
|-
| {{nbsp}}{{nbsp}}[[Dextroamphetamine]] || 6.6–7.2 || 5.8–24.8 || 698–1,765 || <ref name="RothmanBaumannDersch2001">{{cite journal | vauthors = Rothman RB, Baumann MH, Dersch CM, Romero DV, Rice KC, Carroll FI, Partilla JS | title = Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin | journal = Synapse | volume = 39 | issue = 1 | pages = 32–41 | date = January 2001 | pmid = 11071707 | doi = 10.1002/1098-2396(20010101)39:1<32::AID-SYN5>3.0.CO;2-3 | url = }}</ref><ref name="BaumannPartillaLehner2013">{{cite journal | vauthors = Baumann MH, Partilla JS, Lehner KR, Thorndike EB, Hoffman AF, Holy M, Rothman RB, Goldberg SR, Lupica CR, Sitte HH, Brandt SD, Tella SR, Cozzi NV, Schindler CW | title = Powerful cocaine-like actions of 3,4-methylenedioxypyrovalerone (MDPV), a principal constituent of psychoactive 'bath salts' products | journal = Neuropsychopharmacology | volume = 38 | issue = 4 | pages = 552–562 | year = 2013 | pmid = 23072836 | pmc = 3572453 | doi = 10.1038/npp.2012.204 }}</ref>
|-
| {{nbsp}}{{nbsp}}[[Levoamphetamine]] || 9.5 || 27.7 || {{abbr|ND|No data}} || <ref name="Forsyth2012">{{cite journal | vauthors = Forsyth AN | title=Synthesis and Biological Evaluation of Rigid Analogues of Methamphetamines | website=ScholarWorks@UNO | date=22 May 2012 | url=https://scholarworks.uno.edu/td/1436/ | access-date=4 November 2024}}</ref><ref name="Blough2008">{{cite book | vauthors = Blough B | chapter = Dopamine-releasing agents | veditors = Trudell ML, Izenwasser S | title = Dopamine Transporters: Chemistry, Biology and Pharmacology | pages = 305–320 | date = July 2008 | isbn = 978-0-470-11790-3 | oclc = 181862653 | ol = OL18589888W | publisher = Wiley | location = Hoboken [NJ] | doi = | url = https://books.google.com/books?id=QCagLAAACAAJ | chapter-url = https://bitnest.netfirms.com/external/Books/Dopamine-releasing-agents_c11.pdf }}</ref>
|-
| [[Methamphetamine]] || {{Abbr|ND|No data}} || {{Abbr|ND|No data}} || {{Abbr|ND|No data}} || {{Abbr|ND|No data}}
|-
| {{nbsp}}{{nbsp}}[[Dextromethamphetamine]] || 12.3–13.8 || 8.5–24.5 || 736–1,292 || <ref name="RothmanBaumannDersch2001" /><ref name="BaumannAyestasPartilla2012">{{cite journal | vauthors = Baumann MH, Ayestas MA, Partilla JS, Sink JR, Shulgin AT, Daley PF, Brandt SD, Rothman RB, Ruoho AE, Cozzi NV | title = The designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue | journal = Neuropsychopharmacology | volume = 37 | issue = 5 | pages = 1192–1203 | year = 2012 | pmid = 22169943 | pmc = 3306880 | doi = 10.1038/npp.2011.304 }}</ref>
|-
| {{nbsp}}{{nbsp}}[[Levomethamphetamine]] || 28.5 || 416 || 4,640 || <ref name="RothmanBaumannDersch2001" />
|-
| Cathinone || 23.6–25.6 || 34.8–83.1 || 6,100–7,595 || <ref name="Blough2008" /><ref name="BloughDeckerLandavazo2019">{{cite journal | vauthors = Blough BE, Decker AM, Landavazo A, Namjoshi OA, Partilla JS, Baumann MH, Rothman RB | title = The dopamine, serotonin and norepinephrine releasing activities of a series of methcathinone analogs in male rat brain synaptosomes | journal = Psychopharmacology | volume = 236 | issue = 3 | pages = 915–924 | date = March 2019 | pmid = 30341459 | pmc = 6475490 | doi = 10.1007/s00213-018-5063-9 }}</ref><ref name="FitzgeraldGannonWalther2024">{{cite journal | vauthors = Fitzgerald LR, Gannon BM, Walther D, Landavazo A, Hiranita T, Blough BE, Baumann MH, Fantegrossi WE | title = Structure-activity relationships for locomotor stimulant effects and monoamine transporter interactions of substituted amphetamines and cathinones | journal = Neuropharmacology | volume = 245 | issue = | pages = 109827 | date = March 2024 | pmid = 38154512 | doi = 10.1016/j.neuropharm.2023.109827 | pmc = 10842458 | url = }}</ref>
|-
| {{nbsp}}{{nbsp}}{{Small|D}}-Cathinone || 72.0 || 184 || >10,000 || <ref name="HutsellBaumannPartilla2016">{{cite journal | vauthors = Hutsell BA, Baumann MH, Partilla JS, Banks ML, Vekariya R, Glennon RA, Negus SS | title = Abuse-related neurochemical and behavioral effects of cathinone and 4-methylcathinone stereoisomers in rats | journal = Eur Neuropsychopharmacol | volume = 26 | issue = 2 | pages = 288–297 | date = February 2016 | pmid = 26738428 | pmc = 5331761 | doi = 10.1016/j.euroneuro.2015.12.010 | url = }}</ref>
|-
| {{nbsp}}{{nbsp}}{{Small|L}}-Cathinone || 12.4–28 || 18–24.6 || 2,366–9,267 || <ref name="RothmanVuPartilla2003">{{cite journal | vauthors = Rothman RB, Vu N, Partilla JS, Roth BL, Hufeisen SJ, Compton-Toth BA, Birkes J, Young R, Glennon RA | title = In vitro characterization of ephedrine-related stereoisomers at biogenic amine transporters and the receptorome reveals selective actions as norepinephrine transporter substrates | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 307 | issue = 1 | pages = 138–145 | date = October 2003 | pmid = 12954796 | doi = 10.1124/jpet.103.053975 | s2cid = 19015584 }}</ref><ref name="ShalabiWaltherBaumann2017">{{cite journal | vauthors = Shalabi AR, Walther D, Baumann MH, Glennon RA | title = Deconstructed Analogues of Bupropion Reveal Structural Requirements for Transporter Inhibition versus Substrate-Induced Neurotransmitter Release | journal = ACS Chem Neurosci | volume = 8 | issue = 6 | pages = 1397–1403 | date = June 2017 | pmid = 28220701 | pmc = 7261150 | doi = 10.1021/acschemneuro.7b00055 | url = }}</ref><ref name="HutsellBaumannPartilla2016" />
|-
| [[Methcathinone]] || 22–26.1 || 12.5–49.9 || 2,592–5,853 || <ref name="Blough2008" /><ref name="BloughDeckerLandavazo2019" /><ref name="Shalabi2017">{{cite thesis | vauthors = Shalabi AR | title=Structure-Activity Relationship Studies of Bupropion and Related 3-Substituted Methcathinone Analogues at Monoamine Transporters | publisher = Virginia Commonwealth University | via = VCU Scholars Compass | date=14 December 2017 | doi=10.25772/M4E1-3549 | url=https://scholarscompass.vcu.edu/etd/5176/ | access-date=24 November 2024}}</ref><ref name="WaltherShalabiBaumann2019">{{cite journal | vauthors = Walther D, Shalabi AR, Baumann MH, Glennon RA | title = Systematic Structure-Activity Studies on Selected 2-, 3-, and 4-Monosubstituted Synthetic Methcathinone Analogs as Monoamine Transporter Releasing Agents | journal = ACS Chem Neurosci | volume = 10 | issue = 1 | pages = 740–745 | date = January 2019 | pmid = 30354055 | pmc = 8269283 | doi = 10.1021/acschemneuro.8b00524 | url = }}</ref><ref name="FitzgeraldGannonWalther2024" />
|-
| {{nbsp}}{{nbsp}}{{Small|D}}-Methcathinone || {{abbr|ND|No data}} || {{abbr|ND|No data}} || {{abbr|IA|Inactive}} || <ref name="Davies2019">{{cite thesis | vauthors = Davies RA | title=Structure-Activity Relationship Studies of Synthetic Cathinones and Related Agents | publisher = Virginia Commonwealth University Virginia Commonwealth Universityvcu| via = VCU Scholars Compass | date=10 July 2019 | doi=10.25772/TZSA-0396 | url=https://scholarscompass.vcu.edu/etd/5953/ | access-date=24 November 2024}}</ref>
|-
| {{nbsp}}{{nbsp}}{{Small|L}}-Methcathinone || 13.1 || 14.8 || 1,772 || <ref name="RothmanVuPartilla2003" /><ref name="GlennonDukat2017">{{cite book | vauthors = Glennon RA, Dukat M | title = Neuropharmacology of New Psychoactive Substances (NPS) | chapter = Structure-Activity Relationships of Synthetic Cathinones | series = Current Topics in Behavioral Neurosciences | volume = 32 | pages = 19–47 | date = 2017 | publisher = Springer | pmid = 27830576 | pmc = 5818155 | doi = 10.1007/7854_2016_41 | isbn = 978-3-319-52442-9 | chapter-url = }}</ref>
|-
| [[Cathine]] || 15.0 || 68.3 || >10,000 || <ref name="RothmanVuPartilla2003" />
|-
| colspan="5" style="width: 1px; background-color:#eaecf0; text-align: center;" | '''Notes:''' The smaller the value, the more strongly the drug releases the neurotransmitter. The [[bioassay|assay]]s were done in rat brain [[synaptosome]]s and human [[potency (pharmacology)|potencies]] may be different. See also [[Monoamine releasing agent#Activity profiles|Monoamine releasing agent § Activity profiles]] for a larger table with more compounds. '''Refs:''' <ref name="RothmanBaumann2003">{{cite journal | vauthors = Rothman RB, Baumann MH | title = Monoamine transporters and psychostimulant drugs | journal = Eur J Pharmacol | volume = 479 | issue = 1–3 | pages = 23–40 | date = October 2003 | pmid = 14612135 | doi = 10.1016/j.ejphar.2003.08.054 | url = }}</ref><ref name="RothmanBaumann2006">{{cite journal | vauthors = Rothman RB, Baumann MH | title = Therapeutic potential of monoamine transporter substrates | journal = Current Topics in Medicinal Chemistry | volume = 6 | issue = 17 | pages = 1845–1859 | year = 2006 | pmid = 17017961 | doi = 10.2174/156802606778249766 | url = https://zenodo.org/record/1235860 }}</ref>
|}

Cathinone has been found to stimulate the release of [[dopamine]] and inhibit the reuptake of [[epinephrine]], [[norepinephrine]] and [[serotonin]] in the [[central nervous system]] (CNS). These [[neurotransmitters]] are all considered [[monoamine]]s and share the general structure of an [[aromatic ring]] and an [[amine]] group attached by a two-carbon separator.<ref name="Al-Motarreb"/> Because cathinone is a [[hydrophobic]] molecule, it can easily cross cell membranes and other barriers, including the [[blood–brain barrier]].<ref name="Hugins"/> This property allows it to interact with the monoamine transporters in the [[synaptic cleft]] between [[neurons]]. Cathinone induces the release of [[dopamine]] from brain striatal preparations that are prelabelled either with dopamine or its precursors.<ref name="pmid6791236">{{cite journal | vauthors = Kalix P | title = Cathinone, an alkaloid from khat leaves with an amphetamine-like releasing effect | journal = Psychopharmacology | volume = 74 | issue = 3 | pages = 269–270 | year = 1981 | pmid = 6791236 | doi = 10.1007/BF00427108 | s2cid = 20621923 }}</ref> It is more specifically a [[norepinephrine–dopamine releasing agent]] (NDRA) similarly to [[amphetamine]].<ref name="RothmanBaumann2003" /><ref name="RothmanBaumann2006" />

The metabolites of cathinone, cathine and norephedrine, also possess CNS stimulation, but create much weaker effects.<ref name="drugbank">{{cite web|title=Cathinone|url=http://www.drugbank.ca/drugs/DB01560|website=Drug Bank|access-date=10 March 2015|url-status=live|archive-url=https://web.archive.org/web/20150423165202/http://www.drugbank.ca/drugs/DB01560|archive-date=23 April 2015}}</ref> The effects of cathinone on the body can be countered by a preceding administration of a [[dopamine receptor antagonist]].<ref name="drugbank"/> The antagonist prevents synaptic dopamine released by cathinone from  exerting its effect by binding to dopamine receptors.

Cathinone can also affect cholinergic concentrations in the gut and airways by blocking prejunctional [[adrenergic receptor]]s (α<sub>2</sub> adrenergic) and activating [[5-HT7]] receptors, thereby inhibiting [[smooth muscle]] contraction.<ref name="Hugins">{{cite web| vauthors = Hugins KB |title=Cathinone: History, Synthesis, and Human Applications|url=http://www.slideshare.net/KevinHugins/cathinone-history-synthesis-and-human-applications|website=slideshare|date=17 July 2014|access-date=8 March 2015|url-status=live|archive-url=https://web.archive.org/web/20150704030825/http://www.slideshare.net/KevinHugins/cathinone-history-synthesis-and-human-applications|archive-date=4 July 2015}}</ref> It can also induce dry mouth, blurred vision and increased blood pressure and heart rate.<ref name="Al-Motarreb"/>

Cathinone is a weak agonist of the mouse, rat, and human [[trace amine-associated receptor 1]] (TAAR1).<ref name="GainetdinovHoenerBerry2018">{{cite journal | vauthors = Gainetdinov RR, Hoener MC, Berry MD | title = Trace Amines and Their Receptors | journal = Pharmacol Rev | volume = 70 | issue = 3 | pages = 549–620 | date = July 2018 | pmid = 29941461 | doi = 10.1124/pr.117.015305 | url = | doi-access = free }}</ref><ref name="SimmlerBuchyChaboz2016">{{cite journal | vauthors = Simmler LD, Buchy D, Chaboz S, Hoener MC, Liechti ME | title = In Vitro Characterization of Psychoactive Substances at Rat, Mouse, and Human Trace Amine-Associated Receptor 1 | journal = J Pharmacol Exp Ther | volume = 357 | issue = 1 | pages = 134–144 | date = April 2016 | pmid = 26791601 | doi = 10.1124/jpet.115.229765 | url = https://web.archive.org/web/20250509235235/https://d1wqtxts1xzle7.cloudfront.net/74120533/eae6c6e62565b82d46b4d111bbea0f77b9c2-libre.pdf?1635931703=&response-content-disposition=inline%3B+filename%3DIn_Vitro_Characterization_of_Psychoactiv.pdf&Expires=1746838268&Signature=Sy4fJ90yUhxs68314NxYsW5PAaNrBGePRu35WRR4PIF-3YC7Z~sLdnCn5wfqqbLg9bDEGdt~oW55ugMP3D3jgA0BoRI~~GOb0NQOwrtfUEQK1PQs1uuN9qg5Y1ct8z5NsABm44RgtukkwRMdU6fO7OlfIsQ68hOiFk129Ll7UYqldxD2f1xhE2fTTfsxSpb8cMCJzHn7-ItqLdwnAUPFK7WggDIjmY1kCnaHLwIxMwdJCAq8L6DYzSTg7pZkbR8qlou~GXbTPQt~gYpyZTJp5hgW-7V6K5wLlQ7Z2xE7B0f9wEfuc1W1QNafg125Tr-vvAe4LEGKXV58bnn1bpfWKw__&Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA}}</ref> In contrast to cathinone however, most other [[substituted cathinone|cathinone]]s are not human TAAR1 agonists.<ref name="KuropkaZawadzkiSzpot2023">{{cite journal | vauthors = Kuropka P, Zawadzki M, Szpot P | title = A narrative review of the neuropharmacology of synthetic cathinones-Popular alternatives to classical drugs of abuse | journal = Hum Psychopharmacol | volume = 38 | issue = 3 | pages = e2866 | date = May 2023 | pmid = 36866677 | doi = 10.1002/hup.2866 | url = | quote = Another feature that distinguishes [synthetic cathinones (SCs)] from amphetamines is their negligible interaction with the trace amine associated receptor 1 (TAAR1). Activation of this receptor reduces the activity of dopaminergic neurones, thereby reducing psychostimulatory effects and addictive potential (Miller, 2011; Simmler et al., 2016). Amphetamines are potent agonists of this receptor, making them likely to self‐inhibit their stimulating effects. In contrast, SCs show negligible activity towards TAAR1 (Kolaczynska et al., 2021; Rickli et al., 2015; Simmler et al., 2014, 2016). [...] It is worth noting, however, that for TAAR1 there is considerable species variability in its interaction with ligands, and it is possible that the in vitro activity of [rodent TAAR1 agonists] may not translate into activity in the human body (Simmler et al., 2016). The lack of self‐regulation by TAAR1 may partly explain the higher addictive potential of SCs compared to amphetamines (Miller, 2011; Simmler et al., 2013). }}</ref><ref name="SimmlerBuchyChaboz2016" /> TAAR1 activation may auto-inhibit and constrain the [[monoaminergic]] effects of [[monoamine releasing agent]]s possessing TAAR1 agonism.<ref name="KuropkaZawadzkiSzpot2023" /><ref name="EspinozaGainetdinov2014">{{cite book | vauthors = Espinoza S, Gainetdinov RR | title=Taste and Smell | chapter=Neuronal Functions and Emerging Pharmacology of TAAR1 | series=Topics in Medicinal Chemistry | publisher=Springer International Publishing | publication-place=Cham | volume=23 | date=2014 | isbn=978-3-319-48925-4 | doi=10.1007/7355_2014_78 | pages=175–194 | quote = Interestingly, the concentrations of amphetamine found to be necessary to activate TAAR1 are in line with what was found in drug abusers [3, 51, 52]. Thus, it is likely that some of the effects produced by amphetamines could be mediated by TAAR1. Indeed, in a study in mice, MDMA effects were found to be mediated in part by TAAR1, in a sense that MDMA auto-inhibits its neurochemical and functional actions [46]. Based on this and other studies (see other section), it has been suggested that TAAR1 could play a role in reward mechanisms and that amphetamine activity on TAAR1 counteracts their known behavioral and neurochemical effects mediated via dopamine neurotransmission. }}</ref>

===Pharmacokinetics===
Khat leaves are removed from the plant stalk and are kept in a ball in the cheek and chewed. Chewing releases juices from the leaves, which include the alkaloid cathinone. The absorption of cathinone has two phases: one in the [[buccal mucosa]] and one in the [[stomach]] and [[small intestine]].<ref name="Wilder"/> The stomach and small intestine are very important in the absorption of ingested alkaloids.<ref name="Wilder"/> At approximately 2.3 hours after chewing khat leaves, the maximum concentration of cathinone in blood plasma is reached. The mean residence time is 5.2&nbsp;±&nbsp;3.4 hours.<ref name="Wilder"/> The elimination half-life of cathinone is 1.5&nbsp;±&nbsp;0.8 hours.<ref name="Wilder"/> A two-compartment model for absorption and elimination best describes this data. However, at most, only 7% of the ingested cathinone is recovered in the urine.<ref name="Wilder"/> This indicates that the cathinone is being broken down in the body. Cathinone has been shown to selectively metabolize into R,S-(-)-norephedrine and cathine. The reduction of the [[ketone]] group in cathinone will produce cathine. This reduction is catalyzed by enzymes in the liver. The spontaneous breakdown of cathinone is the reason it must be chewed fresh after cultivation.<ref name="Wilder"/>

===Effects on health===
The first documentation of the khat plant being used in medicine was in a book published by an Arabian physician in the 10th century.<ref name="Al-Motarreb"/> It was used as an [[antidepressant]] because it led to feelings of happiness and excitement. Chronic khat chewing can also create drug dependence, as shown by animal studies.<ref name="Al-Motarreb"/> In such studies, monkeys were trained to push a lever to receive the drug reward. As the monkeys' dependence increased, they pressed the lever at an increasing frequency.<ref name="Al-Motarreb"/>

Khat chewing and the effects of cathinone on the body differ from person to person, but there is a general pattern of behavior that emerges after ingesting fresh cathinone:<ref name="Al-Motarreb"/>

# Feelings of euphoria that last for one to two hours
# Discussion of serious issues and increased [[irritability]]
# Very active imagination
# Depression
# Irritability, [[loss of appetite]] and [[insomnia]]

There are other effects not related to the CNS. The chewer can develop [[constipation]] and [[heartburn]] after a khat session. Long-term effects of cathinone can include [[gum disease]] or [[oral cancer]], [[cardiovascular disease]] and [[Depression (mood)|depression]].<ref name="Al-Motarreb"/> The [[withdrawal symptoms]] of cathinone include [[hot flashes]], [[lethargy]] and a great urge to use the drug for at least the first two days.<ref name="Al-Motarreb"/>

==Chemistry==

===Biosynthesis===
[[File:Non-Beta Oxidative Biosynthesis of Cathinone.png|thumb|Mechanism of the Non-Beta Oxidation pathway for the biosynthesis of S-Cathinone in the Khat plant]]

The synthesis of cathinone in khat begins with L-[[phenylalanine]] and the first step is carried out by L-phenylalanine ammonia lyase (PAL), which cleaves off an ammonia group and creates a carbon-carbon double bond, forming [[cinnamic acid]].<ref name="Hagel"/>  After this, the molecule can either go through a beta-oxidative pathway or a non-beta-oxidative pathway.  The beta-oxidative pathway produces [[benzoyl-CoA]] while the non-beta-oxidative pathway produces [[benzoic acid]].<ref name="Hagel"/>  Both of these molecules can be converted to 1-phenylpropane-1,2-dione by a [[condensation reaction]] catalyzed by a ThDP-dependent enzyme (Thiamine diphosphate-dependent enzyme) with [[pyruvate]] and producing CO<sub>2</sub>.<ref name="Hagel"/>  1-phenylpropane-1,2-dione goes through a transaminase reaction to replace a ketone with an ammonia group to form (S)-cathinone.  (S)-Cathinone can then undergo a reduction reaction to produce the less potent but structurally similar cathine or norephedrine, which are also found in the plant.<ref name="Hagel">{{cite journal | vauthors = Hagel JM, Krizevski R, Kilpatrick K, Sitrit Y, Marsolais F, Lewinsohn E, Facchini PJ | title = Expressed sequence tag analysis of khat (Catha edulis) provides a putative molecular biochemical basis for the biosynthesis of phenylpropylamino alkaloids | journal = Genetics and Molecular Biology | volume = 34 | issue = 4 | pages = 640–646 | date = October 2011 | pmid = 22215969 | pmc = 3229120 | doi = 10.1590/S1415-47572011000400017 }}</ref>

Aside from the beta- and non-beta-oxidative pathways, the biosynthesis of cathinone can proceed through a CoA-dependent pathway. The CoA-dependent pathway is actually a mix between the two main pathways as it starts like the beta-oxidative pathway and then when it loses CoA, it finishes the synthesis in the non-beta-oxidative pathway.  In this pathway, the trans-cinnamic acid produced from L-phenylalanine is ligated to a [[Coenzyme A]] (CoA), just like the beginning of the beta-oxidative pathway.<ref name="Hagel"/> It then undergoes [[hydration reaction|hydration]] at the double bond.  This product then loses the CoA to produce [[benzaldehyde]], an intermediate of the non-beta-oxidative pathway.  Benzaldehyde is converted into benzoic acid and proceeds through the rest of the synthesis.<ref name="Hagel"/>

===Synthetic production===
 {{multiple image
 | width = 300
 | footer = Two mechanism of synthesizing Cathinone
 | image1 = Synthesis of Enantiomerically Pure S-Cathinone.png
 | alt1 = Synthesize enantiomerically pure S-Cathinone
 | caption1 = Synthesize enantiomerically pure S-Cathinone
 | image2 = Cathinone synthesis.svg
 | alt2 = Racemic cathinone from propiophenone via the ''α''-brominated intermediate
 | caption2 = Racemic cathinone from propiophenone via the ''α''-brominated intermediate
 }}
Cathinone can be synthetically produced from propiophenone through a [[Friedel-Crafts]] acylation of propionic acid and benzene.<ref name="Hugins"/>  The resulting [[propiophenone]] can be brominated, and the bromine can be substituted with ammonia to produce a racemic mixture of cathinone. A different synthetic strategy must be employed to produce enantiomerically pure (S)-cathinone.  This synthetic route starts out with the N-acetylation of the [[optically active]] [[amino acid]], S-alanine.<ref name="Hugins"/>  Then, [[phosphorus pentachloride]] (PCl<sub>5</sub>) is used to chlorinate the [[carboxylic acid]] forming an acyl chloride. At the same time, a Friedel-Crafts acylation is preformed on benzene with [[aluminum chloride]] catalyst.  Finally, the [[acetyl]] protecting group is removed by heating with [[hydrochloric acid]] to form enantiomerically pure S-(-)-cathinone.<ref name="Hugins"/>

=== Structure ===
[[File:Bupropion skeletal.svg|thumb|120px|right|Chemical structure of bupropion, a cathinone derivative]]

Cathinone can be extracted from ''[[Catha edulis]]'' (khat), or synthesized from ''α''-bromopropiophenone (which is easily made from [[propiophenone]]). Because cathinone is both a [[primary amine]] and a [[ketone]], it is very prone to [[dimer (chemistry)|dimerization]], especially as a free base isolated from plant matter.<ref name="Oeri2021">{{cite journal | vauthors = Oeri HE | title = Beyond ecstasy: Alternative entactogens to 3,4-methylenedioxymethamphetamine with potential applications in psychotherapy | journal = J Psychopharmacol | volume = 35 | issue = 5 | pages = 512–536 | date = May 2021 | pmid = 32909493 | pmc = 8155739 | doi = 10.1177/0269881120920420 | url = }}</ref><ref name="Shulgin2005">{{cite web| vauthors = Shulgin A |title=4-Hydroxy-5-methoxy-N,N-dimethyltryptamine, Psilocybe mushrooms, Psilocin|url=http://www.cognitiveliberty.org/shulgin/blg/2005/12/4-hydroxy-5-methoxy-nn_07.html|date=7 December 2005|work=Ask Dr. Shulgin Online|access-date=10 September 2013|url-status=live|archive-url=https://web.archive.org/web/20130907234431/http://www.cognitiveliberty.org/shulgin/blg/2005/12/4-hydroxy-5-methoxy-nn_07.html|archive-date=7 September 2013}}</ref> These dimers are [[pharmacological activity|pharmacologically inactive]], and the rapid dimerization reduces active amounts of cathinone in non-fresh khat.<ref name="Oeri2021" /><ref name="Shulgin2005" /> The rapid formation of dimers also applies to other non-''N''-substituted cathinones such as [[methylenedioxycathinone]] (MDC; normethylone).<ref name="Oeri2021" /><ref name="Shulgin2005" />

The structure of cathinone is very similar to that of other molecules. By reducing the ketone, it becomes cathine if it retains its stereochemistry, or norephedrine if its stereochemistry is inverted. Cathine is a less potent version of cathinone and cathinone's spontaneous reduction is the reason that older khat plants are not as stimulating as younger ones.  Cathinone and amphetamine are closely related in that amphetamine is only lacking the ketone C=O group.<ref name="Synthetic Cathinone">{{cite web|title=Synthetic cathinones drug profile|url=http://www.emcdda.europa.eu/publications/drug-profiles/synthetic-cathinones|website=European Monitoring Center for Drugs and Drug Addiction|publisher=EMCDDA|access-date=8 March 2015|url-status=live|archive-url=https://web.archive.org/web/20150317061401/http://www.emcdda.europa.eu/publications/drug-profiles/synthetic-cathinones|archive-date=17 March 2015}}</ref>  Cathinone is structurally related to [[methcathinone]], in much the same way as [[amphetamine]] is related to [[methamphetamine]]. Cathinone differs from amphetamine by possessing a [[ketone]] [[oxygen]] atom (C=O) on the ''β'' (beta) position of the side chain. Advancements in synthesizing cyclic cathinones based on α-tetralone have employed chiral HPLC-CD techniques to determine the absolute configuration of enantiomers, an approach that may contribute to the development of pharmaceutical analogs with antidepressant potential.<ref>{{cite journal | vauthors = Paškan M, Dobšíková K, Kuchař M, Setnička V, Kohout M | title = Synthesis and absolute configuration of cyclic synthetic cathinones derived from α-tetralone | journal = Chirality | volume = 36 | issue = 2 | pages = e23646 | date = February 2024 | pmid = 38353318 | doi = 10.1002/chir.23646 | doi-access = free }}</ref> The corresponding substance [[cathine]], is a less powerful stimulant. The biophysiological conversion from cathinone to cathine is to blame for the depotentiation of [[khat]] leaves over time. Fresh leaves have a greater ratio of cathinone to cathine than dried ones, therefore having more psychoactive effects.

There are many cathinone derivatives that include the addition of an R group to the amino end of the molecule.  Some of these derivatives have medical uses as well.  [[Bupropion]] is one of the most commonly prescribed antidepressants and its structure is Cathinone with a tertiary butyl group attached to the nitrogen and chlorine attached to the benzene ring [[meta- (chemistry)|meta-]] to the main carbon chain.<ref name="Synthetic Cathinone"/>

Other cathinone derivatives are strong psychoactive drugs.  One such drug is [[methylone]], a drug structurally similar to [[MDMA]].
{{clear}}

== See also ==
* [[Bupropion]]
* [[Central nervous system]]
* [[Khat]]
* [[Substituted cathinone]]

== References ==
{{reflist}}

== External links ==
* [http://www.erowid.org/chemicals/cathinone/ Erowid Cathinone Vault] {{Webarchive|url=https://web.archive.org/web/20080622214102/https://www.erowid.org/chemicals/cathinone/ |date=2008-06-22 }}
* [https://www.theguardian.com/israel/Story/0,2763,1296958,00.html Cathinone Popularity Soars in Israel]

{{Stimulants}}
{{Monoamine releasing agents}}
{{TAAR modulators}}
{{Phenethylamines}}
{{Chemical classes of psychoactive drugs}}

[[Category:Cathinones| ]]
[[Category:Amphetamine alkaloids]]
[[Category:Drugs acting on the cardiovascular system]]
[[Category:Euphoriants]]
[[Category:Norepinephrine-dopamine releasing agents]]
[[Category:Phenyl compounds]]
[[Category:Stimulants]]
[[Category:TAAR1 agonists]]