3-Methylmethcathinone

Last updated

3-Methylmethcathinone
3-methylmethcathinone.svg
Clinical data
ATC code
  • None
Legal status
Legal status
Pharmacokinetic data
Bioavailability Oral: 5–9% [2]
Protein binding Low [2]
Elimination half-life 50 min (in pigs) [2]
Identifiers
  • 2-(Methylamino)-1-(3-methylphenyl)propan-1-one
PubChem CID
ChemSpider
UNII
KEGG
CompTox Dashboard (EPA)
Chemical and physical data
Formula C11H15NO
Molar mass 177.247 g·mol−1
3D model (JSmol)
Melting point 193.2 °C (379.8 °F) ± 0.2°C (hydrochloride salt)
Boiling point 280.5 °C (536.9 °F) ± 23.0°C at 760 mm Hg
Solubility in water Sparingly soluble in PBS; slightly soluble in ethanol, dimethyl sulfoxide, and dimethyl formamide. [3]  mg/mL (20 °C)
  • CC1=CC=CC(C(C(C)NC)=O)=C1
  • InChI=1S/C11H15NO/c1-8-5-4-6-10(7-8)11(13)9(2)12-3/h4-7,9,12H,1-3H3
  • Key:QDNXSIYWHYGMCD-UHFFFAOYSA-N

3-Methylmethcathinone (3-MMC), also known as metaphedrone, [4] is a designer drug from the substituted cathinone family. 3-MMC is a monoamine transporter substrate that potently inhibits norepinephrine uptake and displays more pronounced dopaminergic activity relative to serotonergic activity, compared to mephedrone (4-MMC). [5] Unlike some synthetic cathinones, 3-MMC has been evaluated in at least one large mammal study. [2]

Contents

3-MMC is a structural isomer of mephedrone (4-MMC), and is also illegal in most countries that have banned mephedrone. However, 3-MMC has still appeared on the recreational drug market as an alternative to mephedrone, and was first identified being sold in Sweden in 2012. [6]

History

3-MMC was first encountered in Sweden in 2012, [7] it was created as a designer drug following the control in many countries of the related compound mephedrone. It was sold as a research chemical, usually in powdered form. There is no known or reported medical use of 3-MMC, it is primarily used recreationally. Some fatal intoxications have been reported, most involving multiple drugs of abuse. [3]

Chemistry

Structure

3-Methylmethcathinone's IUPAC name is 2-(methylamino)-1-(3-methylphenyl)propan-1-one). It is one of many synthetic cathinones, designer drugs related to amphetamines. It is a structural isomer of mephedrone, and controlled as such. It can also be seen as the β-keto analog of 3-methylmethamphetamine

3-MMC contains a chiral center at the C-2 carbon. Therefore two enantiomers exist, the R and S enantiomer. It is assumed that the S form is more potent due to its similarity to cathinone, but further research is needed to confirm this. [8]

Synthesis

There are several ways to synthesize 3-MMC. One route adapted from Power et al [9] is to add ethylmagnesium bromide to 3-methylbenzaldehyde (I) to form the product 1-(3-methylphenyl)-1-propanol (II). This product is then oxidized by pyridinium chlorochromate (PCC) on silica gel to the ketone (III) and brominated with hydrobromic acid to yield the bromoketone (IV). This bromoketone is reacted with ethanolic methylamine to produce the 3-MMC free base (V), which can be converted to the hydrochloride salt (VI) by addition of ethereal hydrogen chloride (VI). [9]

One possible synthesis, starting from 3-methylbenzaldehyde 3mmc synthesis.svg
One possible synthesis, starting from 3-methylbenzaldehyde


Pharmacology

3-MMC potently inhibits the reuptake of monoamines in the human norepinephrine (NET) and dopamine (DAT) transporters. It also acts as a triple releasing agent of dopamine, serotonin, and norepinephrine, similar to many other cathinones. As a releasing agent, it is more selective for dopamine and especially norepinephrine, suggesting that it has stronger amphetamine-like stimulant properties compared to mephedrone or MDMA. [5]

TransporterEC50 [nM] [10] IC50 [nM]
SERT Tooltip Serotonin transporter2924500
NET Tooltip Norepinephrine transporter2780
DAT Tooltip Dopamine transporter70270


Non-human studies

The oral bioavailability of 3-methylmethcathinone was determined at 7% [2] in one pig study, with peak blood concentrations (Tmax) attained within 5 to 10 minutes, and a relatively short half-life of 50 minutes. Concentration in blood plasma dropped below detectability 24 hours after oral ingestion. Decreased feeding behavior resulted in weight loss for some.

Metabolism

The metabolic pathway of 3-MMC is not well described. Known metabolites include 3-methylephedrine and 3-methylnorephedrine. A possible metabolic pathway is β-keto-reduction followed by N-demethylation. [11]

3-MMC also binds to serotonin 5-HT1A, 5-HT2A, 5-HT2C receptors and adrenergic α1A and α2A receptors. [12]

Toxicity

The dose-response curve of 3-methylmethcathinone in humans is not well described in the literature, likely due to limited academic interest to date. Fatalities have been reported over a wide range of blood concentrations, from 249 and 1600 ng/mL. [13] Toxicokinetics are thought to be similar to those for mephedrone, however.

Recreational use

Effects

3-MMC as prepared for recreational use. 3-MMC.jpg
3-MMC as prepared for recreational use.

As with mephedrone, users of 3-MMC typically report effects such as an elevated mood, pleasant body sensations, feelings of love and empathy, euphoria, greater appreciation of music, heightened libido, and increased confidence and sociability. [14]

Adverse effects range from aggression, dry mouth, and jaw clenching, to more serious effects such as hyponatremia, seizures, hyperthermia and rhabdomyolysis. [14] [7]

Abuse

Due to its short duration and dopaminergic effects, 3-MMC is addictive and commonly abused. Repeated dosing within a sitting is typical, sometimes using different routes. Common self-reported doses range from 50 to 150 mg, up to single 500 mg doses. Intranasal administration, or snorting, is the most common route of administration, followed by oral administration. It can also be administered rectally and injected.

Users may dose repeatedly in order to extend the drugs duration, leading to 0.5—2 gram "sessions" that can span an evening. Single-dose effects last from 30 to 60 minutes, typically peaking around 10-minutes post-dose. In a questionnaire-based study of self-reported 3-MMC users in Slovenia, it was found that 88% of users insufflated the drug while 42% took it orally. The study did not find any instances of users injecting 3-MMC. Moreover, 26% of the users reported taking more than 1.5 grams of 3-MMC in a single sitting and over 50% reported having consumed more than 0.5 grams in a single sitting. [15]

Available forms

3-Methylmethcathinone is commonly encountered as a white/off-white crystalline or pasty solid. It can be found sold in capsules. It is assumed to be a racemic mixture like mephedrone.

In the United States, 3-MMC is illegal as a positional isomer of the controlled substance mephedrone [16] It was explicitly designated as a controlled substance on 13 December 2023. [17]

3-MMC is currently being developed as a medicine by the American biotech company MindMed. They have filed for a patent to use 3-MMC for problems such as social anxiety disorder, post-traumatic stress disorder (PTSD), and as an adjunct in couples therapy. [18]

3-MMC is also undergoing clinical trials for its use in treating menstrual symptoms. [19] A successful trial has been completed in the University of Maastricht. These efforts are led by the small Dutch company Period Pill. [20] The company has filed for patent coverage in Canada, Mexico, Croatia, the United States, Morocco, Japan, Brazil, Poland, Hungary, and Korea.

Since October 2015, 3-MMC is a controlled substance in China. [21]

3-MMC is banned in the Czech Republic. [22]

3-MMC was not banned in 2016 by the United Nations Office on Drugs and Crime (UNODC) after a critical review. [23] However, following its subsequent abuse beginning in 2019, this decision was overturned and it was placed into schedule II of the 1971 convention in March 2023. [1]

Effective 28 October 2021, 3-MMC has been scheduled under the Dutch Opium Law and is therefore illegal in the Netherlands. [24]

3-MMC was given narcotic status in India on 8 February 2024.

See also

Related Research Articles

<span class="mw-page-title-main">Psychopharmacology</span> Study of the effects of psychoactive drugs

Psychopharmacology is the scientific study of the effects drugs have on mood, sensation, thinking, behavior, judgment and evaluation, and memory. It is distinguished from neuropsychopharmacology, which emphasizes the correlation between drug-induced changes in the functioning of cells in the nervous system and changes in consciousness and behavior.

<span class="mw-page-title-main">Methcathinone</span> Psychoactive stimulant

Methcathinone is a monoamine alkaloid and psychoactive stimulant, a substituted cathinone. It is used as a recreational drug due to its potent stimulant and euphoric effects and is considered to be addictive, with both physical and psychological withdrawal occurring if its use is discontinued after prolonged or high-dosage administration. It is usually snorted, but can be smoked, injected, or taken orally.

α-Ethyltryptamine Chemical compound

α-Ethyltryptamine, also known as etryptamine, is an entactogen and stimulant drug of the tryptamine family. It was originally developed and marketed as an antidepressant under the brand name Monase by Upjohn in the 1960s before being withdrawn due to toxicity.

<span class="mw-page-title-main">Butylone</span> Entactogen, psychedelic, and stimulant drug of the phenethylamine class

Butylone, also known as β-keto-N-methylbenzodioxolylbutanamine (βk-MBDB), is an entactogen, psychedelic, and stimulant psychoactive drug of the phenethylamine chemical class. It is the β-keto analogue of MBDB and the substituted methylenedioxyphenethylamine analogue of buphedrone.

<span class="mw-page-title-main">Methylone</span> Group of stereoisomers

Methylone, also known as 3,4-methylenedioxy-N-methylcathinone (MDMC), is an empathogen and stimulant psychoactive drug. It is a member of the amphetamine, cathinone and methylenedioxyphenethylamine classes.

<span class="mw-page-title-main">Methedrone</span> Chemical compound of the cathinone class

Methedrone is a recreational drug of the cathinone chemical class. Chemically, methedrone is closely related to para-methoxymethamphetamine (PMMA), methylone and mephedrone. Methedrone received media attention in 2009 after the death of two young Swedish men. In both cases toxicology analysis showed methedrone was the only drug present in both men during the time of their overdose and subsequent deaths.

<span class="mw-page-title-main">Mephedrone</span> Synthetic stimulant drug

Mephedrone, also known as 4-methylmethcathinone, 4-MMC, and 4-methylephedrone, is a synthetic stimulant drug of the amphetamine and cathinone classes. Slang names include drone, M-CAT, White Magic, meow meow and bubble. It is chemically similar to the cathinone compounds found in the Khat plant of eastern Africa. It comes in the form of tablets or crystals, which users can swallow, snort or inject, producing effects similar to those of MDMA, amphetamines and cocaine.

<span class="mw-page-title-main">Ethcathinone</span> Simulant designer drug

Ethcathinone, also known as ethylpropion or ETH-CAT, is a stimulant drug of the phenethylamine, amphetamine, and cathinone chemical classes. It is an active metabolite of the prodrug diethylcathinone and is fully responsible for its effects. Ethcathinone has been identified as an ingredient in both quasi-legal "party pills", and, along with mephedrone, has also been reported as having been sold as "ecstasy" in the Australian city of Cairns.

<span class="mw-page-title-main">MDAI</span> Chemical compound

MDAI (5,6-methylenedioxy-2-aminoindane) is a drug developed in the 1990s by a team led by David E. Nichols at Purdue University. It acts as a non-neurotoxic and highly selective serotonin releasing agent (SSRA) in vitro and produces entactogen effects in humans.

<span class="mw-page-title-main">Monoamine releasing agent</span> Class of compounds

A monoamine releasing agent (MRA), or simply monoamine releaser, is a drug that induces the release of a monoamine neurotransmitter from the presynaptic neuron into the synapse, leading to an increase in the extracellular concentrations of the neurotransmitter. Many drugs induce their effects in the body and/or brain via the release of monoamine neurotransmitters, e.g., trace amines, many substituted amphetamines, and related compounds.

<span class="mw-page-title-main">Naphyrone</span> Substituted cathinone stimulant drug

Naphyrone, also known as O-2482 and naphthylpyrovalerone, is a substituted cathinone drug derived from pyrovalerone that acts as a triple reuptake inhibitor, producing stimulant effects and has been reported as a novel designer drug. No safety or toxicity data is available on the drug.

<span class="mw-page-title-main">Substituted cathinone</span> Class of chemical compounds

Substituted cathinones, which include some stimulants and entactogens, are derivatives of cathinone. They feature a phenethylamine core with an alkyl group attached to the alpha carbon, and a ketone group attached to the beta carbon, along with additional substitutions. Cathinone occurs naturally in the plant khat whose leaves are chewed as a recreational drug.

<span class="mw-page-title-main">4-Methylethcathinone</span> Stimulant designer drug

4-Methylethcathinone or 4-MEC is a chemical that bears a chemical resemblance to mephedrone. Due to its similarity to mephedrone, it is thought to be a stimulant and entactogen drug of the phenethylamine, amphetamine, and cathinone chemical classes. It has been marketed alone or in mixtures with other substituted cathinones under the name "NRG-2", although other blends such as "NRG-1" may have been more ambiguous with their ingredients.

<span class="mw-page-title-main">3,4-Dimethylmethcathinone</span> Designer stimulant drug

3,4-Dimethylmethcathinone (3,4-DMMC) is a stimulant drug first reported in 2010 as a designer drug analogue of mephedrone, apparently produced in response to the banning of mephedrone, following its widespread abuse in many countries in Europe and around the world. 3,4-DMMC has been seized as a designer drug in Australia. In vitro, 3,4-DMMC was shown to be a monoamine transporter substrate that potently inhibits norepinephrine and serotonin reuptake, and to a lesser extent dopamine reuptake.

A monoamine reuptake inhibitor (MRI) is a drug that acts as a reuptake inhibitor of one or more of the three major monoamine neurotransmitters serotonin, norepinephrine, and dopamine by blocking the action of one or more of the respective monoamine transporters (MATs), which include the serotonin transporter (SERT), norepinephrine transporter (NET), and dopamine transporter (DAT). This in turn results in an increase in the synaptic concentrations of one or more of these neurotransmitters and therefore an increase in monoaminergic neurotransmission.

Bath salts are a group of recreational designer drugs. The name derives from instances in which the drugs were disguised as bath salts. The white powder, granules, or crystals often resemble Epsom salts, but differ chemically. The drugs' packaging often states "not for human consumption" in an attempt to circumvent drug prohibition laws. Additionally, they may be described as "plant food", "powdered cleaner", or other products.

<span class="mw-page-title-main">4-Chloromethcathinone</span> Simulant drug of the cathinone class

4-Chloromethcathinone is a stimulant drug of the cathinone class that has been sold online as a designer drug.

<span class="mw-page-title-main">Mexedrone</span> Stimulant and entactogen drug

Mexedrone is a stimulant and an entactogen drug of the cathinone class that has been sold online as a designer drug. It is the alpha-methoxy derivative of Mephedrone.

<span class="mw-page-title-main">3-Chloromethcathinone</span> Stimulant designer drug

3-Chloromethcathinone, also known as clophedrone or 3-CMC, is a synthetic substance belonging to the cathinone class of psychoactive compounds. It is very similar in structure to other cathinone derivatives like metaphedrone (3-MMC) or clephedrone (4-CMC)., Unlike cathinone, which occurs naturally in the khat plant Catha edulis, 3-CMC is not found in nature and is solely produced through chemical synthesis.,

<span class="mw-page-title-main">2-Methylmethcathinone</span> Stimulant designer drug of the substituted cathinone class

2-Methylmethcathinone (2-MMC), also known as ortomephedrone is a recreational designer drug with stimulant and euphoric effects. It is a substituted cathinone derivative, closely related to better known drugs such as 3-methylmethcathinone and 4-methylmethcathinone (mephedrone). It was first identified in Sweden in 2014, and has subsequently been reported in other European countries such as Poland and Spain.

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