3-Methylmethcathinone

Source: Wikipedia, the free encyclopedia.

3-Methylmethcathinone
Clinical data
ATC code
  • None
Legal status
Legal status
Pharmacokinetic data
BioavailabilityOral: 5%-9%[1]
Protein bindingLow[1]
Elimination half-life50 minutes[1]
Identifiers
  • 2-(Methylamino)-1-(3-methylphenyl)propan-1-one
JSmol)
Melting point193.2 °C (379.8 °F) ± 0.2°C (hydrochloride salt)
Boiling point280.5 °C (536.9 °F) ± 23.0°C at 760 mm Hg
Solubility in waterSparingly soluble in PBS; slightly soluble in ethanol, dimethyl sulfoxide, and dimethyl formamide.[2] 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,[3] 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.[4] Unlike some synthetic cathinones, 3-MMC has been evaluated in at least one large mammal study.[1] 3-MMC is a monoamine transporter substrate that potently inhibits norepinephrine uptake and displays more pronounced dopaminergic vs. serotonergic activity.[5]

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.[2]

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.[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

hydrochloride salt (VI) by addition of ethereal hydrogen chloride (VI).[8]

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Available forms

3-MMC is commonly encountered as a white powder or as solid, white, crystalline rocks. It is also sold in capsules. It is assumed to be a racemic mixture like mephedrone.

Mechanism of action

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

3-MMC strongly binds to serotonin

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

Non-human studies

The oral bioavailability of 3-methylmethcathinone was determined at 7%[1] 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.[10]

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.[11] Toxicokinetics are thought to be similar to those for mephedrone, however.

Effects

Desired effects of 3-MMC use are typically stimulation, pleasurable body sensations, euphoria, enhancement of

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]

Legal status

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]

References

  1. ^
    S2CID 26012927
    .
  2. ^ a b "3-Methylmethcathinone (3-MMC) Critical Review Report" (PDF). World Health Organization. Archived from the original (PDF) on 11 November 2021.
  3. .
  4. ^ "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.
  5. ^
    S2CID 28786127
    .
  6. ^ a b European Monitoring Centre for Drugs and Drug Addiction (EMCDDA), Lisbon, Portugal (European Database on New Drugs)
  7. S2CID 58638238
    .
  8. .
  9. .
  10. .
  11. .
  12. ^ a b "3-Methylmethcathinone". Erowid. Retrieved 11 April 2024.
  13. 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. Dutch government
    . 28 October 2021.