Substituted cathinones, or simply 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.
Substituted cathinones act as monoamine releasing agents and/or monoamine reuptake inhibitors, including norepinephrine, dopamine, and/or serotonin. In contrast to substituted amphetamines, most substituted cathinones do not act as agonists of the human trace amine-associated receptor 1 (TAAR1). This may potentiate their stimulating and addictive effects. In addition, β-keto-substituted phenethylamines, such as βk-2C-B, appear to show dramatically reduced potency and efficacy as serotonin 5-HT2A receptor agonists compared to their non-β-keto-substituted counterparts.
Monoamine release profiles The following is a list of serotonin, dopamine, and norepinephrine releasing profiles for various cathinones, measured in rat brain synaptosomes.
+ Name Serotonin Norepinephrine Dopamine Type References 2-BMC 2837 156 650 NDRA 2-CMC 2815 93 179 NDRA 2-FMC >10000 48.7 NDRA 2-MeO-MC 7220 339 920 NDRA 2-MMC 347–490 53 81–97.9 SNDRA 2-TFMeO-MC >10000 >10000 2-TFMMC (2-TFMAP) 8400–>10000 2200 8000–>10000 SNDRA 3-BCPC PAL-586 621 () 3-BMC 136–137 25 21–28.0 SNDRA 3-CC 567 105 64 SNDRA 3-CCPC (RTI-6037-39) PAL-433 1328 () (–)-3-CCPC PAL-1122 562 () (+)-3-CCPC PAL-1123 733 () 3-CEC PAL-361 3-Cl-4-Me-CPC PAL-820 181 () 3-CMC (clophedrone) PAL-434 211–410 19–54.4 26–46.8 SNDRA 3-CPC PAL-363 () 3-FMC 1460 64.8 NDRA 3-MCPC PAL-588 1067 () 3-MeO-CPC PAL-591 1014 () 3-MeO-MC 306–683 111 109–129 SNDRA 3-MMC 268–292 27 28–70.6 SNDRA 3-TFMeO-MC 188 729 SNDRA 3-TFMMC (3-TFMAP) 297–380 2700 610–1290 SNDRA 3,4-DCCPC PAL-787 356 () 4-BMC (brephedrone) 42.5–60.2 100 59.4 SNDRA 4-CC 128.4 85.1 221.8 SNDRA 4-CCPC PAL-743 1632 () 4-CEC 152.6 5194.0 353.6 SDRA 4-CMC (clephedrone) 71.1–144 44–90.9 42.2–74.7 SNDRA 4-FMC (flephedrone) 1290–1450 62 83.4–119 NDRA 4-MCPC PAL-744 667 () 4-MeO-MC (methedrone) 120–195 111 506–881 SNDRA 4-tBu-MC 942 ( ≈ 50%) 4-TFMeO-MC 118 7510 4-TFMMC (4-TFMAP) 190–270 900 2700–4230 SNRA α-Me-MC (βk-mephentermine; RAD-081) 12860 153 590 NDRA AMAPN 21 55 Amfepramone (diethylpropion) >10000 >10000 >10000 BMAPN 27 34 Buphedrone (βk-MEPEA) PAL-429 411 Bupropion (amfebutamone) () () () NDRI Butylone (βk-MBDB) 330 () () SRA/NDRI Cathinone (C; βk-AMPH) 6100–7595 23.6–25.6 34.8–83.1 NDRA -Cathinone >10000 72.0 183.9 NDRA -Cathinone 2366–9267 12.4–28 18–24.6 NDRA Dibutylone () () DRI EDMC 347 327 496 SNDRA Ephylone () () () (NDRI) Ethcathinone (EC) 1923–2118 88.3–99.3 267.6–>1000 NRA Ethylone (βk-MDEA) 617.4 4251 1122 SNDRA Eutylone (βk-EBDB) 1020 () () SRA/NDRI HHMC 14100 110 90 NDRA HDMI 7210 6340 5840 SNDRA MDC 966 394 370 SNDRA Mephedrone (4-MMC) 118.3–122 58–62.7 49.1–51 SNDRA S(–)-Mephedrone 61 74 R(+)-Mephedrone 1470 31 Methcathinone (MC) 2592–5853 22–26.1 12.5–49.9 NDRA -Methcathinone NRA -Methcathinone 1772 13.1 14.8 NDRA Methylone (MDMC) 234–708 140–270 117–220 SNDRA Mexedrone (4-MMC-MeO) 2525 () () SRA/NDRI Normephedrone (4-MC) 210 100 220 SNDRA R(+)-Normephedrone 179 89 150 SNDRA S(–)-Normephedrone 1592 115 391 NDRA Pentylone 476–1030( ≈ 50%) () () SRA/NDRI Propylone 3128 () 975.9 SDRA
List of substituted cathinones The derivatives may be produced by substitutions at four locations of the cathinone molecule:
R1 = hydrogen, or any combination of one or more alkyl, alkoxy, alkylenedioxy, haloalkyl or halide substituents R2 = hydrogen or any alkyl group R3 = hydrogen, any alkyl group, or incorporation in a cyclic structure R4 = hydrogen, any alkyl group, or incorporation in a cyclic structure
The following table displays notable derivatives that have been reported:Europol 2008 Annual Report on the implementation of Council Decision 2005/387/JHAEuropol 2009 Annual Report on the implementation of Council Decision 2005/387/JHAEuropol 2010 Annual Report on the implementation of Council Decision 2005/387/JHAEuropol 2011 Annual Report on the implementation of Council Decision 2005/387/JHAEuropol 2012 Annual Report on the implementation of Council Decision 2005/387/JHAEuropol 2013 Annual Report on the implementation of Council Decision 2005/387/JHAEuropol 2014 Annual Report on the implementation of Council Decision 2005/387/JHAEuropol 2015 Annual Report on the implementation of Council Decision 2005/387/JHAEuropol 2016 Annual Report on the implementation of Council Decision 2005/387/JHAEuropol 2017 Annual Report on the implementation of Council Decision 2005/387/JHA