Methcathinone: Difference between revisions

'''Methcathinone''' {{IPAc-en|ˌ|m|ɛ|θ|ˈ|k|æ|θ|ᵻ|ˌ|n|oʊ|n}} ('''α-[[methyl]][[amino]]-[[propiophenone]]''' or '''ephedrone''') (sometimes called "'''cat'''" or "'''jeff'''" or "'''catnip'''" or "'''M-Kat'''" or "'''kat'''" or "'''intash'''" ) is a [[monoamine]] [[alkaloid]] and [[psychoactive]] [[stimulant]], a substituted [[cathinone]]. It is used as a [[recreational drug]] due to its potent stimulant and [[euphoria|euphoric]] effects and is considered to be [[Substance use disorder|addictive]], with both physical and psychological withdrawal occurring if its use is discontinued after prolonged or high-dosage administration.<ref name="calkins 2005">{{cite journal | pmid = 8594170 | volume=27 | journal = Journal of Psychoactive Drugs | issue=3 | title = Methcathinone: the next illicit stimulant epidemic? | year=1995 | pages=277–85 |vauthors=Calkins RF, Aktan GB, Hussain KL | doi=10.1080/02791072.1995.10472472}}</ref> It is usually [[Nasal administration|snorted]], but can be smoked, injected, or taken orally.

Circa 1994, the United States government recommended to the [[UN Secretary-General]] that methcathinone should be listed as a [[Convention on Psychotropic Substances#Schedule I|Schedule I controlled substance]] in the [[Convention on Psychotropic Substances]].<ref>[http://www.erowid.org/chemicals/chemicals_law1.shtml Erowid]</ref>. In 1995, following US advice, [[China]] added the drug to its list of prohibited substances and discontinued theits pharmaceutical use of it.<ref>{{Cite news|url=https://www.bbc.com/news/world-asia-china-32812621|title = Chinese professor accused in 'Breaking Bad' drugs plot|work = BBC News|date = 20 May 2015}}</ref>

Methcathinone is a beta-keto ''N''-methylamphetamine and is closely related to the naturally occurring compounds, [[cathinone]] and [[cathine]]. It is also very closely related to [[methamphetamine]], differing by only the β-[[ketone]] substituent and differing from [[amphetamine]] by both a keto and N-methyl substituent. Its carbon skeleton is identical to pseudoephedrine and methamphetamine. It differs from pseudoephedrine in that the hydroxide beta to the aromatic ring is oxidized to a ketone.

Methcathinone production utilizes the [[oxidation]] of [[pseudoephedrine]] or [[ephedrine]], the former being preferred because of much higher yields achieved. Oxidation of [[pseudoephedrine]] to methcathinone requires little [[chemistry]] experience, making it (relatively) easy to synthesize.<ref>[https://web.archive.org/web/20131113024319/http://www.scribd.com/doc/35411/The-Clandestine-Chemists-Notebook The Clandestine Chemists Notebook]</ref>{{unreliable source?|date=September 2014}} [[Potassium permanganate]] (KMnO₄) is most commonly used as the oxidant.

In clandestine laboratories, synthesizing methcathinone using potassium permanganate is considered undesirable because of the low yields and the high toxicity of this oxidant, {{xref|(see [[Manganism|Manganese toxicity]])}}; however, if done in a proper laboratory using the proper procedures potassium permanganate can be a high-yielding reactant. A method that yields more methcathinone is oxidizing (pseudo)ephedrine with [[Jones oxidation|chromium (VI)]] compounds, which are far more toxic than permanganate compounds.

Methcathinone as free base is very unstable; it easily loses its [[ketone]] group, which is substituted with a [[hydroxyl]] group, yielding [[pseudoephedrine]], in the reverse of the typical synthesis reaction. Structurally, this occurs when the C=O bond at the Rβ-position is converted into a C-OH bond. Additionally, a dimerization reaction has been observed in solutions of freebase methcathinone, which yields a biologically inactive compound.<ref>{{Cite journal | url=http://chromsci.oxfordjournals.org/content/32/12/552.full.pdf+html | doi=10.1093/chromsci/32.12.552| title=Methcathinone and Designer Analogues: Synthesis, Stereochemical Analysis, and Analytical Properties| journal=Journal of Chromatographic Science| volume=32| issue=12| pages=552–564| year=1994| last1vauthors =Deruiter| first1=DeRuiter J.|, last2=Hayes| first2=L.|, last3=Valaer| first3=A.|, last4=Clark| first4=C.CR, R.| last5=Noggle| first5=F.FT T.}}</ref>

Methcathinone hydrochloride [[hyperlocomotion|increases spontaneous rodent [[Animallocomotor locomotion|locomotoractivity]] activity,<ref name="pmid3575369">{{cite journal |vauthors=Glennon RA, Yousif M, Naiman N, Kalix P |title=Methcathinone: a new and potent amphetamine-like agent |journal=Pharmacol. Biochem. Behav. |volume=26 |issue=3 |pages=547–51 |year=1987 |pmid=3575369 |doi=10.1016/0091-3057(87)90164-X|s2cid=5890314 }}</ref> potentiates the release of [[dopamine]] from [[dopaminergic|dopaminergic nerve]] terminals in the [[brain]],<ref name="pmid3575369" /> and causes [[appetite suppression]].{{Citation needed|date=April 2007}} Users can easily forget to consume fluids leading to increased thirst and dehydration. The effects of methcathinone are similar to those of [[methamphetamine]], initially deemed to be less intense by the inexperienced user, and often more euphoric.{{Citation needed|date=April 2010}} The effects have been compared to those of [[cocaine]], since it commonly causes [[hypertension]] (elevated blood pressure) and [[tachycardia]] (elevated heart rate).

Methcathinone has very strong affinities for the dopamine transporter and the norepinephrine (noradrenaline) transporter. Its affinity for the serotonin transporter is less than that of methamphetamine.<ref>{{cite journal | authorvauthors = Rothman RB, B.Vu N, Partilla JS, Roth BL, Hufeisen SJ, Compton-Toth BA, Birkes J, Young R., Glennon RA | display-authors = 6 | title = In Vitrovitro Characterizationcharacterization of Ephedrineephedrine-Relatedrelated Stereoisomersstereoisomers at Biogenicbiogenic Amineamine Transporterstransporters and the Receptoromereceptorome Revealsreveals Selectiveselective Actionsactions as Norepinephrinenorepinephrine Transportertransporter Substratessubstrates | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 307 | issue = 1 | pages = 138–145 | date =June October 2003 | pmid = 12954796 | doi = 10.1124/jpet.103.053975 | pages = 138–45 | pmid = 12954796| s2cid = 19015584 |display-authors=etal}}</ref>

Anecdotal reports have provided some information on patterns of methcathinone use. The most common [[route of administration]] is via [[human nose|nasal]] [[Insufflation (medicine)|insufflation]] (snorting).{{Citation needed|date=April 2007}} Other routes of administration include ''[[per os|oral]]'', [[intravenous injection|IV injection]] and [[Tobacco smoking|smoking]].

Methcathinone binges resemble amphetamine binges in that the user may not sleep or eat, and takes in little in the way of liquids. The methcathinone binge is followed by long periods of sleep, excess eating, long-lasting nosebleeds ([[Insufflation (medicine)|insufflation]] of methcathinone is corrosive to the [[nasal mucosa]] in the same manner as its methamphetamine counterpart) and, in some cases, [[clinical depression|depression]].{{Citation needed|date=April 2007}}

In preclinical studies, methcathinone [[hydrochloride]] produces an abuse potential similar to that of the [[amphetamines]].<ref>{{cite journal | pmid = 8029273 | volume=47 | issue=4 | title=Intravenous self-injection of methcathinone in the baboon |date=April 1994 | pages=981–3 |vauthors=Kaminski BJ, Griffiths RR | journal=Pharmacol. Biochem. Behav. | doi=10.1016/0091-3057(94)90307-7| s2cid=40584010 | doi-access=free }}</ref>

Methcathinone can be highly psychologically addictive, and can produce a [[methamphetamine]]-like withdrawal, which is somewhat less in intensity than [[methamphetamine]].{{citation needed|date=January 2013}}

In [[psychoactive drug|drug]] [[discrimination studies]] studies, methcathinone hydrochloride evokes responses similar to those induced by both [[Dextroamphetamine|dextroamphetaminedextro{{shy}}amphetamine sulfate]] and [[cocaine]] hydrochloride. When examined in particular pharmacological assays for [[psychomotor agitation|psychomotor]] [[stimulant]]-like activity, both the [[dextrorotary]] and [[levorotary]] [[enantiomeric]] forms of methcathinone hydrochloride have been found to be pharmacologically active. In these assays, the l-form of methcathinone is more active than either d-methcathinone or dextroamphetamine (this is notable as the dextrorotary isomer is the more active isomer of both amphetamine and methamphetamine).

Injecting this substance has recently been associated with symptoms similar to those seen in patients with [[Parkinson's disease]] ([[manganism]]) due to the compound [[manganese dioxide]] which is a byproduct of synthesis with [[permanganate]].<ref>{{cite journal |vauthors=De Bie RM, Gladstone RM, Strafella AP, Ko JH, Lang AE |date=Jun 2007 | title = Manganese-induced Parkinsonism associated with methcathinone (Ephedrone) abuse | url = | journal = Archives of Neurology | volume = 64 | issue = 6| pages = 886–9 | pmid = 17562938 | doi=10.1001/archneur.64.6.886| doi-access = free }}</ref>

TheIn the [[ConventionUnited on Psychotropic SubstancesStates]] lists, methcathinone is listed as a [[Controlled Substances Act#Schedule_I_controlled_substances|Schedule I]] drug, for which there is no clinical substanceuse.<ref>{{cite web|url=httpshttp://www.unodcdrugfree.org/pdfdrug-guide/convention_1971_en.pdfmethcathinone |title=ConventionMethcathinone on- PsychotropicPartnership Substances,for Drug-Free Kids 1971|last=|first=|date=|website=|publisher=United Nations Office on Drugs andDrugfree.org Crime|archiveaccess-urldate=|archive2015-date=|accessdate=9 January 201312-23}}</ref>

* In the [[Netherlands]], methylcathinonemethcathinone is listed as a Level I substance of the [[Opium Law]], for which there is no clinical use.