Methylone

Methylone

Systematic (IUPAC) name
(±)-2-Methylamino-1-(3,4-methylenedioxyphenyl)propan-1-one
Clinical data
Legal status	AU: Unscheduled CA: Unscheduled DE: Anlage II UK: Class B US: Schedule I I-P(Poland)[1]
Routes of administration	Oral, Insufflation, Rectal
Identifiers
CAS Number	186028-79-5 N (racemic) 191916-41-3 (+)
ATC code	None
PubChem	CID 27281606
ChemSpider	21106350 Y
Chemical data
Formula	C11H13NO3
Molar mass	207.23 g/mol
SMILES CC(NC)C(=O)C1=CC=C(OCO2)C2=C1
InChI 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 Y Key:VKEQBMCRQDSRET-UHFFFAOYSA-N Y
Physical data
Solubility in water	357 mg/mL (20 °C)
NY (what is this?)  (verify)

Methylone, also known as M1, 3,4-methylenedioxy-N-methylcathinone, MDMC, bk-MDMA is an entactogen and central nervous system (CNS) stimulant of the phenethylamine, amphetamine, cathinone and methylenedioxyphenethylamine classes. It was first synthesized by chemists Peyton Jacob III and Alexander Shulgin in 1996 for potential use as an antidepressant.^[2] Methylone is a close structural analog of MDMA, differing by the addition of a β-ketone group.^[3]

Recreational use

"Explosion"

At the end of 2004, a new designer drug called "Explosion" appeared in the Netherlands. This drug was sold as a liquid via the internet and in Dutch "smartshops". The stores were selling chemicals that, at the time, were non-scheduled, but which usually became illegal within a year of becoming well-known. These included psychoactive substances such as Salvia divinorum, Psilocybin mushrooms and other MDMA substitutes like BZP and TFMPP. The product was advertised as a "room odorizer" and was sold in plastic tubes containing 5 mL of liquid. The tubes cost between €10 and €15 ($13–$20) and did not present any information about the ingredients of Explosion; they had only a label that read, "Room odorizer Vanilla. Do not ingest" and "Keep away from children. Never use more than one bottle". Users have mentioned ingesting the liquid to reach euphoric stimulating effects similar to those of MDMA. The label circumvented Dutch regulations for illicit drugs and psychoactive substances when intentionally used for intoxication. Analysis of "Explosion" has confirmed that the active ingredient is methylone.^[4] Many other formulations marketed as household chemicals, as well as the pure powder, have been sold.

Effects

Reported dosages range from 100 to 250 mg orally.^[5] Some respondents say that increasing dose with methylone beyond 100–180 mg causes increased physical effects and does not substantially improve the empathic cognitive effects.^[5]

The effects of methylone may include the following:

Central nervous system

• Stimulation
• Euphoria or dysphoria, and anxiolysis or anxiogenesis, depending on the individual.
• An increase in sociability.
• Insomnia and restlessness
• Derealization/depersonalization, hallucinations, and psychosis, depending on the individual, and in all individuals with high dosage or extended use.
• Amblyopia

Sympathomimetic

• Tachycardia and hypertension
• Hyperthermia and sweating
• Mydriasis and nystagmus
• Trismus and bruxism
• Anorexia
• Nausea and vomiting
• Short term erectile dysfunction

Most of these effects are very similar to those of other psychostimulants.

Resemblance to 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 rats trained to discriminate MDMA from saline. Methylone does not substitute for amphetamine or for the hallucinogenic DOM in animals trained to discriminate between these drugs and saline.^[6] 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.^[7][8][3]

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:^[9]

"[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."

Pharmacology

Pharmacodynamics

Methylone acts as a mixed reuptake inhibitor/releasing agent of serotonin, norepinephrine, and dopamine.^[3][10] In comparison to MDMA, it has approximately 3x lower affinity for the serotonin transporter, while its affinity for the norepinephrine and dopamine transporters is similar.^[3][10] Notably, methylone's affinity for the vesicular monoamine transporter 2 (VMAT2) is about 13x lower than that of MDMA.^[3] 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 has relatively robust releasing capabilities,^[10] perhaps due to its ability to phosphorylate the monoamine transporters being similar in potency relative to MDMA.

Pharmacokinetics

The two major metabolic pathways in mammals for methylone are N-demethylation to methylenedioxycathinone (MDC), and demethylation followed by O-methylation of the 3- or 4-hydroxy group to 4-hydroxy-3-methoxymethcathinone (HMMC) or 3-hydroxy-4-methoxymethcathinone (3-OH-4-MeO-MC). When 5 mg/kg of methylone was administered to rats, it was found that around 26% was excreted as HMMC within the first 48 hours (less than 3% excreted unchanged).^[11]

Legal status

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, as such, 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.^[12] 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.^[13][14]

UK

In the UK, 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 compounds was banned immediately.^[15]

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.^[16] Methylone was first classified by Sveriges riksdags health ministry Statens folkhälsoinstitut as "health hazard" under the act Lagen om förbud mot vissa hälsofarliga varor (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).^[17]

Canada

Although not listed as a Schedule 1 ^[18] 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.^[19] 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.^[20]

United States

As of October 21, 2011 the DEA has issued an emergency ban on methylone. It is illegal to possess and distribute.^[21][22]

• 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-methoxymethcathinon, 3-fluoromethcathinone, and 4-fluoromethcathinone as media attention on products labeled as "bath salts" grew. These chemicals are now Schedule I under Florida law.

• Louisiana:

In January 2011, Louisiana Governor Bobby Jindal emergency scheduled 3,4-methylenedioxymethcathinone (methylone), 3,4-methyenedioxypyrovalerone (MDPV), 4-methylmethcathinone (mephedrone), 4-methoxymethcathinone (methedrone), 4-fluoromethcathinone (flephedrone), and 3-fluoromethcathinone (3-FMC).

• Tennessee:

On May 5, 2011, Tennessee Governor Bill Haslam signed a law making it a crime to knowingly produce, manufacture, distribute, sell, offer for sale or possess with intent produce, manufacture, distribute, sell, or offer for sale any product containing 3,4-methylenedioxymethcathinone (methylone), 3,4-methyenedioxypyrovalerone (MDPV), 4-methylmethcathinone (mephedrone), 4-methoxymethcathinone (methedrone), 4-fluoromethcathinone (flephedrone), and 3-fluoromethcathinone (3-FMC).^[23]

• 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. As of 4/12/2013 the DEA placed Methylone as a Schedule 1 substance under the CSA.^[24]

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 bk-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 bk-MDEA and bk-MBDB have become the established names for those substances.

See also

• Substituted cathinone

References