4-Methylcathinone

Last updated
4-Methylcathinone
4-Methylcathinone.png
4-MethylCathinone.png
Clinical data
Other names4-MC; Normephedrone; NSC-60487
Legal status
Legal status
  • DE: NpSG (Industrial and scientific use only)
  • UK: Class B
Identifiers
  • 2-amino-1-(4-methylphenyl)propan-1-one
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
Formula C10H13NO
Molar mass 163.220 g·mol−1
3D model (JSmol)
  • CC1=CC=C(C=C1)C(=O)C(C)N
  • InChI=1S/C10H13NO/c1-7-3-5-9(6-4-7)10(12)8(2)11/h3-6,8H,11H2,1-2H3
  • Key:OHULHWHSUJEYIT-UHFFFAOYSA-N

4-Methylcathinone (4-MC), also known as normephedrone is a stimulant drug of the cathinone group. It is an active metabolite of the better known drug mephedrone (4-methylmethcathinone or 4-MMC). [1] [2] [3] [4]

4-MC is a serotonin–norepinephrine–dopamine releasing agent (SNDRA) similarly to mephedrone. [5] [6] [7] It displays a 2.4-fold selectivity to promote monoamine release via DAT over SERT as opposed to 309-fold selectivity for cathinone. [6] It also releases norepinephrine. [6]

Monoamine release of 4-methylcathinone and related agents (EC50 Tooltip Half maximal effective concentration, nM)
Compound NE Tooltip Norepinephrine DA Tooltip Dopamine 5-HT Tooltip SerotoninRef
Dextroamphetamine 6.6–7.25.8–24.8698–1,765 [8] [9]
Dextromethamphetamine 12.3–13.88.5–24.5736–1,292 [8] [10]
4-Methylamphetamine 22.244.153.4 [11] [12] [13]
4-Methylmethamphetamine 66.941.367.4 [14] [15]
MDMA 54.1–11051.2–27849.6–72 [8] [10] [16] [17] [13] [18]
Cathinone 23.6–25.634.8–83.16,100–7,595 [13] [19] [20]
Methcathinone 22–26.112.5–49.92,592–5,853 [13] [19] [21] [22] [20]
Normephedrone 100220210 [5] [6] [7]
  R(+)-Normephedrone89150179 [7] [6]
  S(–)-Normephedrone1153911,592 [7] [6]
Mephedrone 58–62.749.1–51118.3–122 [10] [9] [19] [22] [23]
  S(–)-MephedroneND7461 [7] [24]
  R(+)-MephedroneND311,470 [7] [24]
Methylone 140–270117–220234–708 [10] [9] [15] [25] [26]
Notes: The smaller the value, the more strongly the drug releases the neurotransmitter. The assays were done in rat brain synaptosomes and human potencies may be different. See also Monoamine releasing agent § Activity profiles for a larger table with more compounds. Refs: [27] [28]

See also

References

  1. ↑ "nor-Mephedrone". Cayman Chemical. Retrieved 27 June 2015.
  2. ↑ Meyer MR, Wilhelm J, Peters FT, Maurer HH (June 2010). "Beta-keto amphetamines: studies on the metabolism of the designer drug mephedrone and toxicological detection of mephedrone, butylone, and methylone in urine using gas chromatography-mass spectrometry". Analytical and Bioanalytical Chemistry. 397 (3): 1225–33. doi:10.1007/s00216-010-3636-5. PMID   20333362. S2CID   21471611.
  3. ↑ Pedersen AJ, Reitzel LA, Johansen SS, Linnet K (June 2013). "In vitro metabolism studies on mephedrone and analysis of forensic cases". Drug Testing and Analysis. 5 (6): 430–8. doi:10.1002/dta.1369. PMID   22573603.
  4. ↑ Dargan PI, Sedefov R, Gallegos A, Wood DM (July–August 2011). "The pharmacology and toxicology of the synthetic cathinone mephedrone (4-methylmethcathinone)". Drug Testing and Analysis. 3 (7–8): 454–63. doi:10.1002/dta.312. PMID   21755604.
  5. 1 2 Mayer FP, Wimmer L, Dillon-Carter O, Partilla JS, Burchardt NV, Mihovilovic MD, Baumann MH, Sitte HH (September 2016). "Phase I metabolites of mephedrone display biological activity as substrates at monoamine transporters". Br J Pharmacol. 173 (17): 2657–2668. doi:10.1111/bph.13547. PMC   4978154 . PMID   27391165.
  6. 1 2 3 4 5 6 Hutsell BA, Baumann MH, Partilla JS, Banks ML, Vekariya R, Glennon RA, Negus SS (February 2016). "Abuse-related neurochemical and behavioral effects of cathinone and 4-methylcathinone stereoisomers in rats". Eur Neuropsychopharmacol. 26 (2): 288–297. doi:10.1016/j.euroneuro.2015.12.010. PMC   5331761 . PMID   26738428.
  7. 1 2 3 4 5 6 Glennon RA, Dukat M (2017). "Structure-Activity Relationships of Synthetic Cathinones". Neuropharmacology of New Psychoactive Substances (NPS). Current Topics in Behavioral Neurosciences. Vol. 32. pp. 19–47. doi:10.1007/7854_2016_41. ISBN   978-3-319-52442-9. PMC   5818155 . PMID   27830576.{{cite book}}: |journal= ignored (help)
  8. 1 2 3 Rothman RB, Baumann MH, Dersch CM, Romero DV, Rice KC, Carroll FI, Partilla JS (January 2001). "Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin". Synapse. 39 (1): 32–41. doi:10.1002/1098-2396(20010101)39:1<32::AID-SYN5>3.0.CO;2-3. PMID   11071707.
  9. 1 2 3 Baumann MH, Partilla JS, Lehner KR, Thorndike EB, Hoffman AF, Holy M, Rothman RB, Goldberg SR, Lupica CR, Sitte HH, Brandt SD, Tella SR, Cozzi NV, Schindler CW (2013). "Powerful cocaine-like actions of 3,4-methylenedioxypyrovalerone (MDPV), a principal constituent of psychoactive 'bath salts' products". Neuropsychopharmacology. 38 (4): 552–562. doi:10.1038/npp.2012.204. PMC   3572453 . PMID   23072836.
  10. 1 2 3 4 Baumann MH, Ayestas MA, Partilla JS, Sink JR, Shulgin AT, Daley PF, Brandt SD, Rothman RB, Ruoho AE, Cozzi NV (2012). "The designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue". Neuropsychopharmacology. 37 (5): 1192–1203. doi:10.1038/npp.2011.304. PMC   3306880 . PMID   22169943.
  11. ↑ Wee S, Anderson KG, Baumann MH, Rothman RB, Blough BE, Woolverton WL (May 2005). "Relationship between the serotonergic activity and reinforcing effects of a series of amphetamine analogs". The Journal of Pharmacology and Experimental Therapeutics. 313 (2): 848–854. doi:10.1124/jpet.104.080101. PMID   15677348. S2CID   12135483.
  12. ↑ Forsyth AN (22 May 2012). "Synthesis and Biological Evaluation of Rigid Analogues of Methamphetamines". ScholarWorks@UNO. Retrieved 4 November 2024.
  13. 1 2 3 4 Blough B (July 2008). "Dopamine-releasing agents" (PDF). In Trudell ML, Izenwasser S (eds.). Dopamine Transporters: Chemistry, Biology and Pharmacology. Hoboken [NJ]: Wiley. pp. 305–320. ISBN   978-0-470-11790-3. OCLC   181862653. OL   18589888W.
  14. ↑ Solis E, Partilla JS, Sakloth F, Ruchala I, Schwienteck KL, De Felice LJ, Eltit JM, Glennon RA, Negus SS, Baumann MH (September 2017). "N-Alkylated Analogs of 4-Methylamphetamine (4-MA) Differentially Affect Monoamine Transporters and Abuse Liability". Neuropsychopharmacology. 42 (10): 1950–1961. doi:10.1038/npp.2017.98. PMC   5561352 . PMID   28530234.
  15. 1 2 Sakloth, Farhana (11 December 2015). Psychoactive synthetic cathinones (or 'bath salts'): Investigation of mechanisms of action. VCU Scholars Compass (Thesis). doi:10.25772/AY8R-PW77 . Retrieved 24 November 2024.
  16. ↑ Marusich JA, Antonazzo KR, Blough BE, Brandt SD, Kavanagh PV, Partilla JS, Baumann MH (February 2016). "The new psychoactive substances 5-(2-aminopropyl)indole (5-IT) and 6-(2-aminopropyl)indole (6-IT) interact with monoamine transporters in brain tissue". Neuropharmacology. 101: 68–75. doi:10.1016/j.neuropharm.2015.09.004. PMC   4681602 . PMID   26362361.
  17. ↑ Setola V, Hufeisen SJ, Grande-Allen KJ, Vesely I, Glennon RA, Blough B, Rothman RB, Roth BL (June 2003). "3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") induces fenfluramine-like proliferative actions on human cardiac valvular interstitial cells in vitro". Molecular Pharmacology. 63 (6): 1223–1229. doi:10.1124/mol.63.6.1223. PMID   12761331. S2CID   839426.
  18. ↑ Brandt SD, Walters HM, Partilla JS, Blough BE, Kavanagh PV, Baumann MH (December 2020). "The psychoactive aminoalkylbenzofuran derivatives, 5-APB and 6-APB, mimic the effects of 3,4-methylenedioxyamphetamine (MDA) on monoamine transmission in male rats". Psychopharmacology (Berl). 237 (12): 3703–3714. doi:10.1007/s00213-020-05648-z. PMC   7686291 . PMID   32875347.
  19. 1 2 3 Blough BE, Decker AM, Landavazo A, Namjoshi OA, Partilla JS, Baumann MH, Rothman RB (March 2019). "The dopamine, serotonin and norepinephrine releasing activities of a series of methcathinone analogs in male rat brain synaptosomes". Psychopharmacology. 236 (3): 915–924. doi:10.1007/s00213-018-5063-9. PMC   6475490 . PMID   30341459.
  20. 1 2 Fitzgerald LR, Gannon BM, Walther D, Landavazo A, Hiranita T, Blough BE, Baumann MH, Fantegrossi WE (March 2024). "Structure-activity relationships for locomotor stimulant effects and monoamine transporter interactions of substituted amphetamines and cathinones". Neuropharmacology. 245: 109827. doi:10.1016/j.neuropharm.2023.109827. PMC  10842458. PMID   38154512.
  21. ↑ Shalabi, Abdelrahman R. (14 December 2017). Structure-Activity Relationship Studies of Bupropion and Related 3-Substituted Methcathinone Analogues at Monoamine Transporters. VCU Scholars Compass (Thesis). doi:10.25772/M4E1-3549 . Retrieved 24 November 2024.
  22. 1 2 Walther D, Shalabi AR, Baumann MH, Glennon RA (January 2019). "Systematic Structure-Activity Studies on Selected 2-, 3-, and 4-Monosubstituted Synthetic Methcathinone Analogs as Monoamine Transporter Releasing Agents". ACS Chem Neurosci. 10 (1): 740–745. doi:10.1021/acschemneuro.8b00524. PMC   8269283 . PMID   30354055.
  23. ↑ Bonano JS, Banks ML, Kolanos R, Sakloth F, Barnier ML, Glennon RA, Cozzi NV, Partilla JS, Baumann MH, Negus SS (May 2015). "Quantitative structure-activity relationship analysis of the pharmacology of para-substituted methcathinone analogues". Br J Pharmacol. 172 (10): 2433–2444. doi:10.1111/bph.13030. PMC   4409897 . PMID   25438806.
  24. 1 2 Gregg RA, Baumann MH, Partilla JS, Bonano JS, Vouga A, Tallarida CS, Velvadapu V, Smith GR, Peet MM, Reitz AB, Negus SS, Rawls SM (February 2015). "Stereochemistry of mephedrone neuropharmacology: enantiomer-specific behavioural and neurochemical effects in rats". Br J Pharmacol. 172 (3): 883–894. doi:10.1111/bph.12951. PMC   4301696 . PMID   25255824.
  25. ↑ Glatfelter GC, Walther D, Evans-Brown M, Baumann MH (April 2021). "Eutylone and Its Structural Isomers Interact with Monoamine Transporters and Induce Locomotor Stimulation". ACS Chem Neurosci. 12 (7): 1170–1177. doi:10.1021/acschemneuro.0c00797. PMC   9423000 . PMID   33689284.
  26. ↑ Elmore JS, Dillon-Carter O, Partilla JS, Ellefsen KN, Concheiro M, Suzuki M, Rice KC, Huestis MA, Baumann MH (February 2017). "Pharmacokinetic Profiles and Pharmacodynamic Effects for Methylone and Its Metabolites in Rats". Neuropsychopharmacology. 42 (3): 649–660. doi:10.1038/npp.2016.213. PMC   5240186 . PMID   27658484.
  27. ↑ Rothman RB, Baumann MH (October 2003). "Monoamine transporters and psychostimulant drugs". Eur J Pharmacol. 479 (1–3): 23–40. doi:10.1016/j.ejphar.2003.08.054. PMID   14612135.
  28. ↑ Rothman RB, Baumann MH (2006). "Therapeutic potential of monoamine transporter substrates". Current Topics in Medicinal Chemistry. 6 (17): 1845–1859. doi:10.2174/156802606778249766. PMID   17017961.
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