Methylenedioxymethcathinone

{| id="synChemInfoBox" class="wikitable" width="300px" style="float: right; margin: 0 0 .5em .5em;" Methylenedioxymethcathinone
 * bgcolor="#ffffff" align="center" colspan="2" |
 * bgcolor="#ffffff" align="center" colspan="2" |
 * align="center" colspan="2" | IUPAC name:
 * align="center" colspan="2" | IUPAC name:

2-methylamino-1-(3,4-methylenedioxyphenyl)propan-1-one Unscheduled (UK) Unscheduled (CA)
 * - align="center"
 * CAS number Racemic Methylone: 186028-79-5; (S)-Methylone: 191916-41-3
 * ATC code  ?
 * bgcolor="#eeeeee" | Chemical formula
 * C11H13NO3
 * bgcolor="#eeeeee" | Molecular weight
 * 207.23
 * bgcolor="#eeeeee" | Elimination half life
 * bgcolor="#eeeeee" | Legal status
 * Unscheduled (USA)
 * bgcolor="#eeeeee" | Elimination half life
 * bgcolor="#eeeeee" | Legal status
 * Unscheduled (USA)
 * bgcolor="#eeeeee" | Legal status
 * Unscheduled (USA)


 * bgcolor="#eeeeee" | Delivery
 * 150-200mg orally 50-150mg intravenously
 * colspan="2"|Recreational uses:
 * euphoria
 * bonding
 * euphoria
 * bonding


 * colspan="2"|Other uses:
 * Marriage counseling
 * Anxiety
 * PTSD
 * End of Life Care
 * End of Life Care


 * colspan="2"|Contraindications:
 * Not for use in combination with stimulants (amphetamines, large doses of caffeine, etc).
 * Not for use in combination with diuretics (alcohol).
 * Not for use in individuals with high blood pressure, hypertension, or blood clotting disorders.
 * Not for use in individuals who have displayed allergies to amphetamine drugs.
 * Must never be used in combination with MAOI (Monoamine Oxidase Inhibitor) drugs.
 * Must never be used in combination with MAOI (Monoamine Oxidase Inhibitor) drugs.

!colspan="2"|Side effects:
 * colspan="2"|Endocrine:
 * hyponatremia
 * hyponatremia


 * colspan="2"|Eye:
 * mydriasis
 * mydriasis


 * colspan="2"|Psychological:
 * euphoria
 * strong sense of empathy
 * serotonin deficiency
 * serotonin deficiency


 * colspan="2"|Skin:
 * sweaty palms
 * heavy sweating
 * heavy sweating


 * colspan="2"|Miscellaneous:
 * restlessness
 * chattering teeth
 * chattering teeth



Overview


Methylone is a beta-ketone analogue of MDMA (Ecstasy). It is also known as bk-MDMA, M1, or MDMCat. The more intuitive abbreviation MDMC unfortunately can not be used for this chemical, since it had already been given to another earlier Shulgin creation, 3,4-ethylenedioxymethmphetamine (PIHKAL #110). It is more properly known as 3,4-methylenedioxymethcathinone. Methylone is related to methcathinone as MDMA is related to methamphetamine and MDA is to amphetamine. 

In spite of some substantial pharmacokinetic differences (its dopaminergic activity is far more pronounced relative to its serotonergic activity), methylone is an empathogen-like drug and a mild stimulant, producing effects similar to, yet less intense than MDMA.

Explosion
At the end of 2004, a new designer drug called ‘Explosion’ appeared in the Netherlands. This new drug is sold as a liquid via the internet and in Dutch ‘smartshops’, stores selling non-scheduled psychoactive substances. The product is advertised as a ‘room odorizer’ and is sold in plastic tubes containing 5 ml of liquid. The tubes cost between €10 and €15 ($13–$20) and do not present any information about the composition of Explosion; they contain only a label saying ‘Room odorizer Vanilla. Do not ingest’ and ‘Keep away from children. Never use more than one bottle’. In spite of this label, users mention that they ingest the liquid to reach the intended psychoactive effect. The text was probably put onto the label to circumvent Dutch regulations for illicit drugs and psychoactive substances.

Analyses of Explosion have demonstrated that the main ingredient of the liquid is the compound methylone (3,4-methylenedioxymethcathinone or 2-methylamino-1-(3,4-methylenedioxyphenyl)propan-1-one). 3,4-Methylenedioxymethcathinone (MDMCat or methylone) is the benzylic ketone analogue of 3,4-methylenedioxymethamphetamine (MDMA): it contains an additional oxygen atom at the benzylic position of the molecule ( Figure 1). 3,4-Methylenedioxymethcathinone was first synthesized by Alexander Shulgin. Because of the similarity of effects between methamphetamine and its benzylic ketone methcathinone, he examined whether there was a comparable connection between MDMA and its benzylic analogue. He called the new substance methylone. 

MDMA resemblance
Methylone resembles MDMA in its behavioural profile, as 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. Further, also in common with MDMA, methylone acts on monoaminergic systems. In vitro, methylone is threefold less potent than MDMA at inhibiting platelet serotonin accumulation and as potent as MDMA in its inhibiting effects on the dopamine and noradrenaline transporters.

In spite of these behavioural and pharmacological similarities between methylone and MDMA, the observed subjective effects of both drugs are not completely identical (Erowid.org). Shulgin wrote about the effects of this drug: ‘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’ (Cognitiveliberty.org).

Legal Status
In the Netherlands, methylone is not yet scheduled as a drug of abuse, but is considered to be a psychoactive medicine. 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 (van Amsterdam et al., 2004). Until now, no research has been conducted on the toxicity of methylone, so nothing is known about the harmfulness of this new drug.

Methylone is not explicitly scheduled in the United States, but possession may still result in prosecution under the Federal Analog Act as an MDMA analogue. 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 is currently not specifically mentioned in UK law as the beta-ketone is not covered under the Misuse of Phenethylamines Law.

Methylone was sold in New Zealand for around 6 months from November 2005 to April 2006 as an Ecstasy substitute, under the brand name Ease. The product was withdrawn after legal disputes with the government.

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

Combination With MBDB
MDMA has both serotonergic and dopaminergic actions. Methylone does as well, but the dopaminergic activity is much more pronounced. MBDB is another closely related chemical, but its activity is mostly serotonergic. Some people have interpreted this situation as meaning that methylone and MBDB are "split halves" of the effects of MDMA, and have taken the two chemicals together in an attempt to recreate the pharmacology of MDMA. Whether or not the pharmacology of this mixture is comparable to MDMA is unknown, as is the safety of such mixtures.

Naming Problem
While Shulgin assigned the name methylone to this chemical, and that name has become the standard nomenclature, it is a problematic name. The problem is that Methylone® is a trademarked brand name for an injectible form of methylprednisolone, a corticosteroid hormone used to treat arthritis and severe allergic reactions. Aside from context, they can be distinguished by the fact that the name will always be capitalized when referring to the prescription drug.