3-Methylmethcathinone

Last updated

3-Methylmethcathinone
3-methylmethcathinone.svg
Clinical data
ATC code
  • None
Legal status
Legal status
Identifiers
  • 2-(Methylamino)-1-(3-methylphenyl)propan-1-one
PubChem CID
ChemSpider
UNII
KEGG
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 3-MMC is sparingly soluble in PBS; slightly soluble in ethanol, dimethyl sulfoxide, and dimethyl formamide. [1]  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, also known as 3-MMC and metaphedrone, [2] is a designer drug from the substituted cathinone family. 3-MMC is closely related in structure to the more commonly known illicit drug mephedrone (4-MMC), and is also illegal in most countries that have banned mephedrone due to 3-MMC being a structural isomer of 4-MMC. 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. [3] Unlike some synthetic cathinones, 3-MMC has been evaluated in at least one large mammal study. [4] 3-MMC is a monoamine transporter substrate that potently inhibits norepinephrine uptake and displays more pronounced dopaminergic vs. serotonergic activity. [5]

Contents

History

3-MMC was first encountered in Sweden in 2012, [6] 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 powder form. There is no known or reported medical use of 3-MMC and it is being used for recreation. Some fatal intoxications have been reported, most involving multiple drugs of abuse. [1]

Structure

3-Methylmethcathinone (3-MMC) chemical name is 2-(methylamino)-1-(3-methylphenyl)propan-1-one) and is a cathinone derivative, which is a synthetic form of phenylethylamines. 3-MMC has a cathinone which is substituted with a methyl group at the 3 position which makes it a structural isomer of Mephedrone.[ citation needed ]

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 has to be done to confirm this. [7]

Synthesis

There are several ways to synthesize 3-MMC. One of ways to synthesize 3-MMC, which is adapted from Power et al, is to add ethylmagnesium bromide to 3-methylbenzaldehyde (I). The product (II) is then oxidized by pyridinium chlorochromate (PCC) on silica gel to the ketone (III) and brominated with hydrobromic acid to yield the bromo ketone (IV). This bromo ketone 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). [8]

3mmc synthesis.svg

Available forms

The most common form of 3-MMC is as a white crystalline powder or as white solid crystals. Sometimes however it is also sold as capsules filled with 3-MMC. There is no information available whether it is a racemate or enantiomerically pure.

Mechanism of action

3-MMC (like 4-MMC) inhibits norepinephrine (NET), serotonin (SERT) and dopamine (DAT) transport. 3-MMC inhibits NET and DAT more potently than SERT which suggests that 3-MMC has stronger amphetamine-like stimulant properties compared to mephedrone. [5]

3-MMC strongly binds to serotonin 5-HT1A, 5-HT2A and 5-HT2C receptors. In addition, 3-MMC binds weakly to the α1A and α2A adrenergic receptors. [9]

Non-human studies

Metaphedrone oral bioavailability was 7% in rodent studies, with peak blood concentrations (Tmax) attained within 5 to 10 minutes, and a plasma half-life of 0.8 hours. 3-MMC levels dropped below detectable levels after 24 hours of oral ingestion. Decreased feeding behaviour resulted in weight loss in 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. [10]

Toxicity

Metaphedrone dose-response 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. [11] Toxicokinetics are thought to be similar to those for mephedrone, however.

Effects

The desired effects of 3-MMC are stimulation, spontaneous bodily sensations, euphoria, enhancement of empathy, affection and sociability, happiness, awareness which are similar effects of other stimulants. [12] Adverse effects can range from stuttering, fatigue, verbosity, reduced level of consciousness, depression, aggression, delirium and confusion, double vision, difficulty in concentration, headaches, dehydration, hallucinations, fear to more serious effects such as hyponatremia, diaphoresis, seizures, hyperthermia and rhabdomyolysis. [12] [6]

Abuse

3-MMC is taken via inhalation, injection, insufflation or oral administration. Single session repeat dosing is typical, sometimes via different routes. Common self-reported doses range from 50 to 150 mg, up to single 500 mg doses.

Users may dose repeatedly in order to extend effect duration, leading to 0.5 g to 2 g "sessions." Single-dose effects last from 4–6 hours, typically peaking around 2-hours post-dose. In a questionnaire-based study of self-reported 3-MMC users in Slovenia, it was found that 88.8% of users insufflated the drug while 42.6% 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 g of 3-MMC in a single sitting and over 50% reported having consuming more than 0.5 g in a single sitting. [13]

In the United States, 3-MMC is illegal as a positional isomer of the schedule 1 controlled substance Mephedrone (4-MMC). [14] It was explicitly designated as a controlled substance itself on 13 December 2023. [15]

3-MMC is currently being developed as a medicine by a publicly traded company MindMed Inc NASDAQ:MNMD based on a patent titled "Use of 3-methylmethcathinone" [16]

Since October 2015, 3-MMC is a controlled substance in China. [17]

3-MMC is banned in the Czech Republic. [18]

3-MMC was not banned in 2016 by the United Nations Office on Drugs and Crime (UNODC) after a critical review. [19] However, they finally decided to ban it in March of 2023 following recommendations by the WHO. March 2023 – UNODC

Effective 28 October 2021, 3-MMC has been scheduled under the Dutch Opium Law and is therefore illegal in the Netherlands. [20]

Related Research Articles

A designer drug is a structural or functional analog of a controlled substance that has been designed to mimic the pharmacological effects of the original drug, while avoiding classification as illegal and/or detection in standard drug tests. Designer drugs include psychoactive substances that have been designated by the European Union as new psychoactive substances (NPS) as well as analogs of performance-enhancing drugs such as designer steroids. Some of these were originally synthesized by academic or industrial researchers in an effort to discover more potent derivatives with fewer side effects and shorter duration and were later co-opted for recreational use. Other designer drugs were prepared for the first time in clandestine laboratories. Because the efficacy and safety of these substances have not been thoroughly evaluated in animal and human trials, the use of some of these drugs may result in unexpected side effects.

<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">Methylenedioxypyrovalerone</span> Chemical compound

Methylenedioxypyrovalerone (MDPV) is a stimulant of the cathinone class that acts as a norepinephrine–dopamine reuptake inhibitor (NDRI). It was first developed in the 1960s by a team at Boehringer Ingelheim. Its activity at the dopamine transporter is six times stronger than at the norepinephrine transporter and it is virtually inactive at the serotonin transporter. MDPV remained an obscure stimulant until around 2004 when it was reportedly sold as a designer drug. In the US, products containing MDPV and labeled as bath salts were sold as recreational drugs in gas stations, similar to the marketing for Spice and K2 as incense, until it was banned in 2011.

<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.

<i>alpha</i>-Pyrrolidinopentiophenone Chemical compound

α-Pyrrolidinopentiophenone is a synthetic stimulant of the cathinone class developed in the 1960s that has been sold as a designer drug and often consumed for recreational reasons. α-PVP is chemically related to pyrovalerone and is the ketone analog of prolintane.

<span class="mw-page-title-main">Buphedrone</span> Stimulant drug and research chemical

Buphedrone, also known as α-methylamino-butyrophenone (MABP), is a stimulant of the phenethylamine and cathinone chemical classes that was first synthesized in 1928.

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

3-Fluoromethcathinone is a chemical compound of the phenethylamine, amphetamine, and cathinone classes that has been sold online as a designer drug. It is a structural isomer of flephedrone (4-fluoromethcathinone).

<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.

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

Benzedrone (4-MBC) is a designer drug which has been found since 2010 as an ingredient in a number of "bath salt" mixes sold as recreational drugs.

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

Pentedrone is a stimulant of the cathinone class that has been sold as a designer drug and has been found since 2010 as an ingredient in a number of "bath salt" mixes sold as legal highs.

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 mislabeled as plant food, powdered cleaner, and other such products.

<i>N</i>-Ethylbuphedrone Stimulant of the cathinone class

N-Ethylbuphedrone is a stimulant of the cathinone class that has been sold as a designer drug. It is the β-ketone analogue of N,alpha-diethylphenylethylamine.

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

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

<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">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.

References

  1. 1 2 "3-Methylmethcathinone (3-MMC) Critical Review Report" (PDF). World Health Organization. Archived from the original (PDF) on 11 November 2021.
  2. ↑ Preedy V (26 April 2016). Neuropathology of Drug Addictions and Substance Misuse Volume 2: Stimulants, Club and Dissociative Drugs, Hallucinogens, Steroids, Inhalants and International Aspects (2 ed.). London: King's College. ISBN   978-0-12-800212-4.
  3. ↑ "EMCDDA 2012 Annual report on the state of the drugs problem in Europe" (PDF). Archived from the original (PDF) on 23 April 2014. Retrieved 17 April 2014.
  4. ↑ Shimshoni JA, Britzi M, Sobol E, Willenz U, Nutt D, Edery N (June 2015). "3-Methyl-methcathinone: Pharmacokinetic profile evaluation in pigs in relation to pharmacodynamics". Journal of Psychopharmacology. 29 (6): 734–43. doi:10.1177/0269881115576687. PMID   25804420. S2CID   26012927.
  5. 1 2 Luethi D, Kolaczynska KE, Docci L, Krähenbühl S, Hoener MC, Liechti ME (May 2018). "Pharmacological profile of mephedrone analogs and related new psychoactive substances" (PDF). Neuropharmacology. 134 (Pt A): 4–12. doi:10.1016/j.neuropharm.2017.07.026. PMID   28755886. S2CID   28786127.
  6. 1 2 European Monitoring Centre for Drugs and Drug Addiction (EMCDDA), Lisbon, Portugal (European Database on New Drugs)
  7. ↑ Ferreira B, Dias da Silva D, Carvalho F, de Lourdes Bastos M, Carmo H (February 2019). "The novel psychoactive substance 3-methylmethcathinone (3-MMC or metaphedrone): A review". Forensic Science International. 295: 54–63. doi:10.1016/j.forsciint.2018.11.024. PMID   30572220. S2CID   58638238.
  8. ↑ Power JD, McGlynn P, Clarke K, McDermott SD, Kavanagh P, O'Brien J (October 2011). "The analysis of substituted cathinones. Part 1: chemical analysis of 2-, 3- and 4-methylmethcathinone". Forensic Science International. 212 (1–3): 6–12. doi:10.1016/j.forsciint.2011.04.020. PMID   21601387.
  9. ↑ Schmidt KT, Weinshenker D (April 2014). "Adrenaline rush: the role of adrenergic receptors in stimulant-induced behaviors". Molecular Pharmacology. 85 (4): 640–50. doi:10.1124/mol.113.090118. PMC   3965894 . PMID   24499709.
  10. ↑ Frison G, Frasson S, Zancanaro F, Tedeschi G, Zamengo L (August 2016). "Detection of 3-methylmethcathinone and its metabolites 3-methylephedrine and 3-methylnorephedrine in pubic hair samples by liquid chromatography-high resolution/high accuracy Orbitrap mass spectrometry". Forensic Science International. 265: 131–7. doi:10.1016/j.forsciint.2016.01.039. PMID   26901638.
  11. ↑ Ameline A, Dumestre-Toulet V, Raul JS, Kintz P (March 2019). "Determination of a threshold fatal 3-MMC concentration in human: mission impossible". Psychopharmacology. 236 (3): 865–867. doi:10.1007/s00213-018-4941-5. PMID   29876621. S2CID   46978121.
  12. 1 2 "3-Methylmethcathinone". Erowid. Retrieved 11 April 2024.
  13. ↑ Sande M (January 2016). "Characteristics of the use of 3-MMC and other new psychoactive drugs in Slovenia, and the perceived problems experienced by users". The International Journal on Drug Policy. 27: 65–73. doi:10.1016/j.drugpo.2015.03.005. PMID   25908121.
  14. ↑ "Lists of: Scheduling Actions Controlled Substances Regulated Chemicals" (PDF). U.S. Department of Justice. February 2023. Retrieved 5 March 2023.
  15. ↑ "eCFR :: 21 CFD 1308.11 (Dec 12, 2023) -- Schedule I." Electronic Code of Federal Regulations. Retrieved 21 December 2023.
  16. ↑ WO 2019026019,Golan E, Haden M, Van Wettum R,"Use of 3-methylmethcathinone",published 7 February 2019, assigned to Therapeutic Adjuncts Inc.and Recraceutical Corp. B.V.
  17. ↑ "关于印发《非药用类麻醉药品和精神药品列管办法》的通知" (in Chinese). China Food and Drug Administration. 27 September 2015. Archived from the original on 1 October 2015. Retrieved 1 October 2015.
  18. ↑ "Látky, o které byl doplněn seznam č. 4 psychotropních látek (příloha č. 4 k nařízení vlády č. 463/2013 Sb.)" (PDF) (in Czech). Ministerstvo zdravotnictví. Archived from the original (PDF) on 9 March 2016. Retrieved 6 February 2016.
  19. ↑ "Extract from the Report of the 38 th Expert Committee on Drug Dependence, convened from 14 to 18 November 2016, at WHO headquarters in Geneva" (PDF). Commission on Narcotic Drugs. Retrieved 7 December 2016.
  20. ↑ "Designerdrug 3-MMC vanaf vandaag verboden" (in Dutch). Dutch government. 28 October 2021.
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