Methylone

Source: Wikipedia, the free encyclopedia.
"MDMC" redirects here. For other uses, see MDMC (disambiguation).
Not to be confused with ethylone.

Methylone
Clinical data
Other names3,4-Methylenedioxy-N-methylcathinone; 3,4-Methylenedioxymethcathinone; MDMC; MDMCAT; β-Keto-MDMA; βk-MDMA; M1; TSND-201; TSND201; MeONE; EASE; EMM; Explosion
Routes of
administration		Common: oral, insufflation[1]
Uncommon: IV or IM injection, rectal[1]
ATC code
  • None
Legal status
Legal status
Pharmacokinetic data
Onset of action0.5 hours[4]
Elimination half-life5.8–6.9 hours[4]
Duration of action2.5–3.0 hours[4]
Identifiers
  • 1-(1,3-Benzodioxol-5-yl)-2-(methylamino)propan-1-one
JSmol)
Solubility in water357 mg/mL (20 °C)
SMILES
  • CC(NC)C(=O)C1=CC=C(OCO2)C2=C1
  • InChI=1S/C11H13NO3/c1-7(12-2)11(13)8-3-4-9-10(5-8)15-6-14-9/h3-5,7,12H,6H2,1-2H3 checkY
  • Key:VKEQBMCRQDSRET-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Methylone, also known as 3,4-methylenedioxy-N-methylcathinone (MDMC), is an

analogue of MDMA.[6][1] Methylone is usually taken orally, but is also used by other routes.[5][1]

The drug acts as a

duration is about 2 to 3 hours.[5][4]

Methylone was first

recreational drug by 2004 and has become a controlled substance in many countries.[6][1] Similarly to MDMA, it is being developed for the treatment of post-traumatic stress disorder (PTSD).[18][19][20]

Chemistry

Methylone is the substituted cathinone analogue of 3,4-methylenedioxymethamphetamine (MDMA) and the 3,4-methylenedioxy analog of methcathinone. The only structural difference of methylone with respect to MDMA is the substitution of 2 hydrogen atoms by 1 oxygen atom in the β position of the phenethylamine core, forming a ketone group.[10]

Effects

Resemblance to MDMA

See also: MDMA
Structural similarities between some amphetamine-like stimulants and their 3,4-methylenedioxy- derivatives.
Left: amphetamine, methamphetamine and methcathinone.
Right: MDA, MDMA, and methylone

Methylone substitutes for MDMA in

DOM in animal drug discrimination tests.[21] Further, also in common with MDMA, methylone acts on monoaminergic systems. In vitro, methylone has one third the potency of MDMA at inhibiting platelet serotonin accumulation and about the same in its inhibiting effects on the dopamine and noradrenaline transporters.[22][23][10]

In spite of these behavioral and pharmacological similarities between methylone and MDMA, the observed subjective effects of both drugs are not completely identical. Alexander Shulgin wrote of the former:[15]

"[Methylone] has almost the same potency of MDMA, but it does not produce the same effects. It has an almost antidepressant action, pleasant and positive, but not the unique magic of MDMA."

In acute pharmacological studies of methylone (50–300 mg) in humans, the drug produced physiological and psychological effects including increased

misuse potential of methylone, as measured by for instance drug liking responses, appeared to be similar to that of MDMA.[24] However it also has less off-target effects than MDMA which may be an advantage for medical applications.[26][24][27]

Pharmacology

Pharmacodynamics

Methylone acts as a mixed

affinity for the serotonin transporter, while its affinity for the norepinephrine and dopamine transporters is similar.[10][28] Notably, methylone's affinity for the vesicular monoamine transporter 2 (VMAT2) is about 13-fold lower than that of MDMA.[10] The results of these differences in pharmacology relative to MDMA are that methylone is less potent in terms of dose, has more balanced catecholaminergic effects relative to serotonergic, and behaves more like a reuptake inhibitor like methylphenidate than a releaser like amphetamine; however, methylone still has relatively robust releasing capabilities.[28]

In contrast to MDMA, methylone and its

trace amine-associated receptor 1 (TAAR1).[32][14]

Methylone has been found to produce

preclinical research and showed greater effects than MDMA.[33]

Similarly to MDMA, methylone has been found to be a

dopaminergic neurotoxicity in rodents.[11] However, in one study, moderate doses of MDMA produced serotonergic neurotoxicity in rodents whereas methylone and mephedrone did not do so, suggesting that cathinones like methylone may be less neurotoxic than their corresponding amphetamine counterparts like MDMA.[12][7]

EC50
Tooltip Half maximal effective concentration, nM)
Compound 5-HTTooltip Serotonin NETooltip Norepinephrine DATooltip Dopamine Ref
Dextroamphetamine 698–1,765 6.6–7.2 5.8–24.8 [34][8]
Dextromethamphetamine
 736–1,292 12.3–13.8 8.5–24.5 [34][7]
MDA
Tooltip Methylenedioxyamphetamine		 160–162 47–108 106–190 [35][36][37]
MDMA
Tooltip Methylenedioxymethamphetamine		 49.6–72 54.1–110 51.2–278 [34][7][38][35][37]
Cathinone 6,100–7,595 23.6–25.6 34.8–83.1 [36][39][40]
Methcathinone 2,592–5,853 22–26.1 12.5–49.9 [36][39][41][42][40]
MDCTooltip Methylenedioxycathinone 966 394 370 [9]
Methylone (MDMC) 234–708 140–270 117–220 [7][8][43][44][9]
Mephedrone 118.3–122 58–62.7 49.1–51 [7][8][39][42][45]
Notes: The smaller the value, the more strongly the drug releases the neurotransmitter. The assays were done in rat brain synaptosomes and human potencies may be different. See also Monoamine releasing agent § Activity profiles for a larger table with more compounds. Refs: [46][47]

Pharmacokinetics

The two major

duration of action of methylone in humans are 0.5 hours and 2.5 to 3.0 hours, respectively.[4]

History

Methylone was first

recreational drug by 2004.[6][1] It has become a controlled substance in many countries.[1]

Society and culture

Methylone in powder form

Names and etymology

"Methylone" is also a trademarked brand name for an injectable form of methylprednisolone, a corticosteroid hormone used to treat arthritis and severe allergic reactions; hence, methylone may be confused with it. Aside from context, they can be distinguished by the fact that the name will usually be capitalized when referring to the prescription drug.

A proposed alternate name is βk-MDMA, or beta-keto-MDMA. While this nomenclature has not caught on because the name "methylone" became widely used before the conflicting Methylone trademark was noticed, the analogous names for related chemicals

βk-MBDB
have become the established names for those substances.

Commercial distribution

Bottles of Explosion

Analysis of "Explosion" has confirmed that the active ingredient is methylone.[50][unreliable source?] Many other formulations marketed as household chemicals, as well as the pure powder, have been sold.

Netherlands

In the Netherlands, methylone is not yet listed under the Opium Law, but is covered under the medicine act. Because methylone is not registered officially, it is forbidden to trade in methylone. The Minister of Health has asked the Coordination point Assessment and Monitoring new drugs group (CAM) to gather information about this substance, resulting possibly in an official risk assessment.[51] Until now, no research has been conducted on the toxicity of methylone, so nothing is known about the harmfulness of this new drug.

New Zealand

In New Zealand, although methylone is not explicitly scheduled and falls outside the strict definitions of an "amphetamine analogue" in the Misuse of Drugs Act, it is considered to be "substantially similar" to methcathinone and is thus considered by law enforcement authorities to be a Class C illegal drug. Methylone was sold in New Zealand for around 6 months from November 2005 to April 2006 as an MDMA substitute, under the name "Ease". The product was withdrawn after legal disputes with the government.[52][53]

United Kingdom

In the United Kingdom, methylone is illegal since the 16/04/2010 revision of the misuse of drugs act. Before this it was not specifically mentioned in United Kingdom (U.K.) law as the β-ketone was not covered under the Misuse of Drugs Act. In March 2010, plans were announced to make methylone and other cathinones, Class B drugs, "within weeks". While delayed by dissatisfaction in the Advisory Council on the Misuse of Drugs, the revision was rushed through by the government with little regard for the views of the council. The importation of the compound was banned immediately.[54]

Sweden

Sveriges riksdag added methylone to schedule I ("substances, plant materials and fungi which normally do not have medical use") as narcotics in Sweden as of Oct 1, 2010, published by Medical Products Agency in their regulation LVFS 2010:23 listed as Metylon, 2-metylamino-1-(3,4-metylendioxifenyl)propan-1-on.[55] Methylone was first classified by Sveriges riksdags health ministry Statens folkhälsoinstitut [sv] as "health hazard" under the act Lagen om förbud mot vissa hälsofarliga varor [sv] (translated Act on the Prohibition of Certain Goods Dangerous to Health) as of Nov 1, 2005, in their regulation SFS 2005:733 listed as 3,4-metylendioximetkatinon (Metylon).[56]

Canada

Although not listed as a Schedule 1[57] substance, Health Canada reports that methylone falls under the scheduling as an analogue of amphetamine. However, Methylone bears the exact chemical difference between amphetamine and cathinone – and cathinone is listed as not being an analogue of amphetamine, possibly implying that methylone is unscheduled in Canada.[58] The CDSA was updated as a result of the Safe Streets Act changing amphetamines from Schedule 3 to Schedule 1; however, methylone was not added.[59]

United States

In October 2011, the DEA issued an emergency ban on methylone. It was made illegal to possess and distribute.[60][61] On April 4, 2013, the DEA placed methylone as a Schedule 1 substance under the CSA.[62]

  • Arizona:
Effective February 16, 2012, methylenedioxymethcathinone (methylone) was classified as a dangerous drug, making it a felony to knowingly possess, use, possess for sale, manufacture, administer, transport for sale, import into the state, or offer to transport for sale or import into this state, sell, transfer or offer to sell or transfer. A.R.S. 13-3401(6)(c)(xliii), 2012 Ariz. Legis. Serv. Ch. 1 (H.B. 2356).
  • Florida:
In January 2011, it was reported that Florida Attorney General Pam Bondi issued an emergency ban on MDPV, Methylone, Mephedrone, 3-methoxymethcathinone, 3-fluoromethcathinone, and 4-fluoromethcathinone as media attention on products labeled as "bath salts" grew. These chemicals are now Schedule I under Florida law.[63]
  • Louisiana:
In January 2011, Louisiana Governor Bobby Jindal emergency scheduled 3,4-methylenedioxymethcathinone (methylone), 3,4-methyenedioxypyrovalerone (
3-FMC
).
  • Tennessee:
On May 5, 2011, Tennessee Governor
3-FMC).[64]
  • Texas:
In September 2011, Texas added 3,4-methylenedioxy-N-methylcathinone to the Penalty Group 2 listing of the Health and Safety Code. Possession of a substance in penalty group 2 is a minimum of a state jail felony.
  • Michigan:
Schedule 1 controlled substance in 2012.

Research

Post-traumatic stress disorder

Under the developmental code TSND-201, methylone is under development by Transcend Therapeutics for the treatment of post-traumatic stress disorder (PTSD).[18][19][20] As of July 2024, it is in phase 2 clinical trials for this indication.[18][19]

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