Jump to content

3-Methylmethcathinone

From Wikipedia, the free encyclopedia

This is an old revision of this page, as edited by Reba16 (talk | contribs) at 01:50, 28 May 2021. The present address (URL) is a permanent link to this revision, which may differ significantly from the current revision.

3-Methylmethcathinone
Clinical data
ATC code
  • None
Legal status
Legal status
Identifiers
  • 2-(Methylamino)-1-(3-methylphenyl)propan-1-one
CAS Number
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC11H15NO
Molar mass177.247 g·mol−1
3D model (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 water3-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 common illicit drug mephedrone (4-MMC), and is illegal in most countries that have banned mephedrone as it is a structural isomer of it. 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 other legal highs 3-MMC was tested and characterized in large mammals,[4] providing much more knowledge about it than is known about other synthetic cathinones. 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 although only a few involved 3-MMC only.[7]

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.

3-MMC contains a chiral center at the C-2 carbon. Therefore two enantionmers 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.[8]

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 ethyl magnesium bromide to 3-methylbenzaldehyde. The product is then oxidized by pyridinium chlorochromate on silica gel and brominated with hydrobromic acid to yield the bromo ketone. This bromo ketone is reacted with ethanolic methylamine to produce the 3-MMC free base, which can be converted to the hydrochloride salt by addition of ethereal hydrogen chloride.[9]

Reactions

There are no simple conversions into controlled substances.[10]

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

The studies of pharmacology are currently lacking but it was found 3-MMC just like 4-MMC inhibits norepinephrine(NET), serotonin(SERT) and dopamine(DAT) transporters. 3-MMC inhibits SERT and NET and more potently than the DAT which suggests that 3-MMC has stronger amphetamine-like stimulant properties compared to mephedrone.[11]

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.[12]

Metabolism

The metabolism pathway of 3-MMC is not yet fully known. From analysis of human pubic hair of a drug dealer it is known that 3-methylephedrine and 3-methylnorephedrine are metabolites of the drug. A possible metabolic pathway is β-keto-reduction followed by N-demethylation.[13]

Efficacy

Generally, 3-MMC is taken via inhalation, injection, insufflation or oral administration. Repeated use of 3-MMC in a single session, often via different routes, has also been seen. The dosages range from threshold, light, common, strong and heavy corresponding to 50mg, 50-150mg, 150-250mg, 250-350mg and 350+mg respectively. Most self-reported doses range from 50 to 150mg or even up to 500mg. Furthermore, most users report repeated usage in order to extend their euphoric experience often leading to 0.5g to 2g of 3-MMC consumed in one sitting or even within a few hours. The drug lasts from 4-6 hours with its peak being 2-3 hours long. 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 0.5g in a single sitting.[14]

Adverse effects

The desired effects of 3-MMC are stimulation, spontaneous bodily sensations, euphoria, enhancement of empathy, affection and sociability, happiness, awareness and an increased appreciation of music which are similar effects of other amphetamines and drugs of abuse.[15] The 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 hypona-tremia, diaphoresis, seizures, hyperthermia and rhabdomyolysis.[16][17] Chronic 3-MMC abusers can expect their relationships with their friends, partner and family to deteriorate.[18]

Toxicity

Very few cases of overdoses have been recorded in literature for concentrations between 249 and 1600 ng/mL for 3-MMC. Since the concentration range is quite high in the literature, defining the concentration at which impairment or fatality occurs is very difficult. No correlation between the measured concentration and the type of intoxication was found. The most likely cause for this is the chemical instability of the drug.[19]

Effects on animals

In animals, 3-MMC has a rather high absorption rate with the peak concentration being achieved within 5 to 10 minutes after oral ingestion and a plasma half-life of 0.8 hours. The bioavailability was tested to be around 7% and 3-MMC levels dropped below detectable levels after 24 hours of oral ingestion. Moreover, 3-MMC caused a significant change in the feeding behaviour of animals often resulting in weight gain over time. Caution is needed when applying the data for human safety from the extrapolated animal data because of low sample size, lack of data and low dosage.[20]

Legal status

As of 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 by the United Nations Office on Drugs and Crime (UNODC) after a critical review.[23]

3-MMC is currently not covered in the Dutch Opium Law and is therefore legal in the Netherlands. However, the Dutch government is going to add 3-MMC to the banned substance list in the 2nd half of 2021 (for it to be considered as illegal hard drug).[24] [25]

References

  1. ^ https://www.who.int/medicines/access/controlled-substances/4.4_3-MMC_CritReview.pdf
  2. ^ Preedy, Victor (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
  4. ^ Shimshoni, J. A.; Britzi, M.; Sobol, E.; Willenz, U.; Nutt, D.; Edery, N. (24 March 2015). "3-Methyl-methcathinone: Pharmacokinetic profile evaluation in pigs in relation to pharmacodynamics". Journal of Psychopharmacology. 29 (6): 734–743. doi:10.1177/0269881115576687. PMID 25804420. S2CID 26012927.
  5. ^ Luethi D, Kolaczynska KE, Docci L, Krähenbühl S, Hoener MC, Liechti ME (2018). "Pharmacological profile of mephedrone analogs and related new psychoactive substances" (PDF). Neuropharmacology. 15 (134): 4–12. doi:10.1016/j.neuropharm.2017.07.026. PMID 28755886. S2CID 28786127.
  6. ^ European Monitoring Centre for Drugs and Drug Addiction (EMCDDA), Lisbon, Portugal (European Database on New Drugs)
  7. ^ https://www.who.int/medicines/access/controlled-substances/4.4_3-MMC_CritReview.pdf
  8. ^ Bárbara Ferreira, Diana Dias da Silva, Félix Carvalho, Maria de Lourdes Bastos, Helena Carmo. The novel psychoactive substance 3-methylmethcathinone (3-MMC or metaphedrone): A review. Forensic Science International, Volume 295, 2019, Pages 54-63, ISSN 0379-0738, https://doi.org/10.1016/j.forsciint.2018.11.024.
  9. ^ J.D. Power, P. McGlynn, K. Clarke, S.D. McDermott, P. Kavanagh, J. O'Brien. The analysis of substituted cathinones. Part 1: chemical analysis of 2-, 3- and 4-methylmethcathinone. Forensic Sci. Int., 212 (1–3) (2011), pp. 6-12
  10. ^ https://www.who.int/medicines/access/controlled-substances/4.4_3-MMC_CritReview.pdf
  11. ^ Luethi, D., Kolaczynska, K. E., Docci, L., Krähenbühl, S., Hoener, M. C., & Liechti, M. E. (2018). Pharmacological profile of mephedrone analogs and related new psychoactive substances. Neuropharmacology, 134(Pt A), 4–12. https://doi.org/10.1016/j.neuropharm.2017.07.026
  12. ^ K.T. Schmidt, D. Weinshenker, Adrenaline rush: the role of adrenergic receptors in stimulant-induced behaviors, Mol. Pharmacol. 85 (4) (2014) 640–650.
  13. ^ G. Frison, S. Frasson, F. Zancanaro, G. Tedeschi, L. Zamengo, Detection of 3- methylmethcathinone and its metabolites 3-methylephedrine and 3-meth- ylnorephedrine in pubic hair samples by liquid chromatography-high resolution/high accuracy Orbitrap mass spectrometry, Forensic Sci. Int. 265 (2016) 131–137.
  14. ^ Sande M. Characteristics of the use of 3-MMC and other new psychoactive drugs in Slovenia, and the perceived problems experienced by users. Int J Drug Policy. 2016 Jan;27:65-73
  15. ^ https://www.erowid.org/experiences (accessed March 2021)
  16. ^ https://www.erowid.org/experiences (accessed March 2021)
  17. ^ European Monitoring Centre for Drugs and Drug Addiction (EMCDDA), Lisbon, Portugal (European Database on New Drugs)
  18. ^ European Monitoring Centre for Drugs and Drug Addiction (EMCDDA), Lisbon, Portugal (European Database on New Drugs)
  19. ^ Ameline, A., Dumestre-Toulet, V., Raul, J. S., & Kintz, P. (2019). Determination of a threshold fatal 3-MMC concentration in human: mission impossible. Psychopharmacology, 236(3), 865–867. https://doi.org/10.1007/s00213-018-4941-5
  20. ^ J.A. Shimshoni, M. Britzi, E. Sobol, U. Willenz, D. Nutt, N. Edery, 3-Methyl-methcathinone: Pharmacokinetic profile evaluation in pigs in relation to pharmacodynamics, J. Psychopharmacol. 29 (6) (2015) 734–743.
  21. ^ "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.
  22. ^ "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.
  23. ^ "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.
  24. ^ "Kabinet gaat designerdrug 3-MMC verbieden". Retrieved 27 May 2021.
  25. ^ "Wat is 3-MMC?" [What is 3-MMC?]. Drugs en Uitgaan (in Dutch). Trimbos-instituut. Retrieved 25 February 2021. 3-MMC staat niet op de Opiumwet en is dus legaal (onder de Warenwet). [3-MMC is not covered in the Opium Law and is therefore legal (under the Commodities Act).]


Stub icon

This drug article relating to the nervous system is a stub. You can help Wikipedia by expanding it.

Retrieved from "https://en.wikipedia.org/w/index.php?title=3-Methylmethcathinone&oldid=1025520278"