Substituted cathinone
Class of chemical compounds
Cathinone
General chemical structure of substituted cathinones, with R1 -R4 defined in text
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 .[ 1] [ 2] [ 3] [ 4] [ 5] Cathinone occurs naturally in the plant khat whose leaves are chewed as a recreational drug.[ 6]
Substituted cathinones act as monoamine releasing agents and/or monoamine reuptake inhibitors , including of norepinephrine , dopamine , and/or serotonin .[ 7] [ 8] [ 9] [ 10] [ 11] [ 12] In contrast to substituted amphetamines , substituted cathinones do not act as agonists of the human trace amine-associated receptor 1 (TAAR1).[ 13] [ 14] [ 15] This may potentiate their stimulating and addictive effects.[ 13] [ 14] 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.[ 16]
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:[ 17] [ 18] [ 19] [ 20] [ 21] [ 22] [ 23] [ 24] [ 25] [ 26] [ 27] [ 28] [ 29] [ 30] [ 31] [ 32] [ 33] [ 34] [ 35] [ 36] [ 37] [ 38]
Structure
Compound
R1
R2
R3
R4
CAS number
Cathinone
H
Me
H
H
71031-15-7
Methcathinone
H
Me
H
Me
5650-44-2
Ethcathinone
H
Me
H
Et
51553-17-4
Propylcathinone
H
Me
H
nPr
52597-14-5
Buphedrone
H
Et
H
Me
408332-79-6
N-Ethylbuphedrone (NEB )
H
Et
H
Et
1354631-28-9
N-Methyl-N-ethylbuphedrone
H
Et
Me
Et
Pentedrone
H
nPr
H
Me
879722-57-3
N-Ethylpentedrone
H
nPr
H
Et
18268-16-1
N-Isopropylpentedrone
H
nPr
H
iPr
18268-14-9
Hexedrone
H
nBu
H
Me
2169446-41-5
N-Ethylhexedrone
H
nBu
H
Et
18410-62-3
N-Butylhexedrone
H
nBu
H
nBu
18296-66-7
N-Isobutylhexedrone (NDH)
H
nBu
H
i -Bu
Isohexedrone
H
iBu
H
Me
N-Ethylheptedrone
H
nPe
H
Et
Octedrone
H
hexyl
H
Me
Dimethylcathinone
H
Me
Me
Me
15351-09-4
Diethylpropion
H
Me
Et
Et
134-80-5
N-Methyl-N-ethylcathinone
H
Me
Me
Et
1157739-24-6
Bupropion
3-Cl
Me
H
t -Bu
34911-55-2
Hydroxybupropion
3-Cl
Me
H
2-Me-3-OH-propan-2-yl
357399-43-0
Mephedrone
4-Me
Me
H
Me
1189805-46-6
2-MMC
2-Me
Me
H
Me
1246911-71-6
2-MEC
2-Me
Me
H
Et
1439439-84-5
2-EMC
2-Et
Me
H
Me
2-EEC
2-Et
Me
H
Et
2446466-59-5
3-MMC
3-Me
Me
H
Me
1246816-62-5
3-MEC
3-Me
Me
H
Et
1439439-83-4
3-MPC
3-Me
Me
H
nPr
3-EMC
3-Et
Me
H
Me
3-EEC
3-Et
Me
H
Et
2446466-61-9
4-EMC
4-Et
Me
H
Me
1225622-14-9
4-EEC
4-Et
Me
H
Et
2446466-62-0
4-MC
4-Me
Me
H
H
31952-47-3
Benzedrone
4-Me
Me
H
Bn
1225617-75-3
2'-MeO-Benzedrone
4-Me
Me
H
2-MeO-Bn
2,N-Dimethylbenzedrone
2-Me
Me
Me
Bn
3,N-Dimethylbenzedrone
3-Me
Me
Me
Bn
4,N-Dimethylbenzedrone
4-Me
Me
Me
Bn
4-MEC
4-Me
Me
H
Et
1225617-18-4
4-MPC
4-Me
Me
H
nPr
N,N-DMMC
4-Me
Me
Me
Me
1448845-14-4
N,N-MEMC
4-Me
Me
Me
Et
N,N-DEMC
4-Me
Me
Et
Et
676316-90-8
4-MEAP
4-Me
Pr
H
Et
746540-82-9
EDMC
4-Et
Me
Me
Me
2,3-DMMC
2,3-dimethyl
Me
H
Me
2,3-DMEC
2,3-dimethyl
Me
H
Et
2,4-DMMC
2,4-dimethyl
Me
H
Me
1225623-63-1
2,4-DMEC
2,4-dimethyl
Me
H
Et
1225913-88-1
2,5-DMMC
2,5-dimethyl
Me
H
Me
2,5-DMEC
2,5-dimethyl
Me
H
Et
2,6-DMMC
2,6-dimethyl
Me
H
Me
2,6-DMEC
2,6-dimethyl
Me
H
Et
3,4-DMMC
3,4-dimethyl
Me
H
Me
1082110-00-6
3,4-DMEC
3,4-dimethyl
Me
H
Et
1225811-81-3
3,5-DMEC
3,5-dimethyl
Me
H
Et
2,4,5-TMMC
2,4,5-trimethyl
Me
H
Me
1368603-85-3
2,4,5-TMOMC
2,4,5-trimethoxy
Me
H
Me
3,4,5-TMOMC
3,4,5-trimethoxy
Me
H
Me
Methedrone
4-MeO
Me
H
Me
530-54-1
Dimethedrone
4-MeO
Me
Me
Me
91564-39-5
Ethedrone
4-MeO
Me
H
Et
2-MOMC
2-MeO
Me
H
Me
3-MOMC
3-MeO
Me
H
Me
1435933-70-2
3-FC
3-F
Me
H
H
1082949-91-4
4-FC
4-F
Me
H
H
80096-51-1
2-FMC
2-F
Me
H
Me
1186137-35-8
2-FEC
2-F
Me
H
Et
3-FMC
3-F
Me
H
Me
1049677-77-1
3-FEC
3-F
Me
H
Et
2-CMC
2-Cl
Me
H
Me
2-BMC
2-Br
Me
H
Me
2-IMC
2-I
Me
H
Me
2-TFMAP
2-CF3
Me
H
Me
Clophedrone (3-CMC)
3-Cl
Me
H
Me
1049677-59-9
3-CEC
3-Cl
Me
H
Et
2150476-60-9
3-BMC
3-Br
Me
H
Me
676487-42-6
3-IMC
3-I
Me
H
Me
3-TFMAP
3-CF3
Me
H
Me
Flephedrone
4-F
Me
H
Me
447-40-5
4-FEC
4-F
Me
H
Et
1225625-74-0
Clephedrone (4-CMC)
4-Cl
Me
H
Me
1225843-86-6
2-CEC
2-Cl
Me
H
Et
4-CEC
4-Cl
Me
H
Et
14919-85-8
2-CiPC
2-Cl
Me
H
iPr
3-CiPC
3-Cl
Me
H
iPr
4-CiPC
4-Cl
Me
H
iPr
4-CBC
4-Cl
Me
H
nBu
1225621-71-5
2-CDMC
2-Cl
Me
Me
Me
3-CDMC
3-Cl
Me
Me
Me
4-CDMC
4-Cl
Me
Me
Me
1157667-29-2
Brephedrone
4-Br
Me
H
Me
486459-03-4
4-BEC
4-Br
Me
H
Et
135333-26-5
4-IMC
4-I
Me
H
Me
4-TFMAP
4-CF3
Me
H
Me
4-EFMC
4-(2-fluoroethyl)
Me
H
Me
4-MTMC
4-SCH3
Me
H
Me
4-MSMC
4-SO2 CH3
Me
H
Me
4-PHMC
4-phenyl
Me
H
Me
Mexedrone
4-Me
methoxymethyl
H
Me
FMMC
3-F-4-Me
Me
H
Me
1696642-00-8
MFMC
3-Me-4-F
Me
H
Me
1368943-21-8
4-Cl-3-MMC
3-Me-4-Cl
Me
H
Me
MMOMC
3-Me-4-MeO
Me
H
Me
3,4-DCMC
3,4-dichloro
Me
H
Me
802281-39-6
3,4-DCEC
3,4-dichloro
Me
H
Et
1225618-63-2
3,5-DCMC
3,5-dichloro
Me
H
Me
3,5-DFMC
3,5-difluoro
Me
H
Me
1430343-55-7
2,5-DMOMC
2,5-dimethoxy
Me
H
Me
βk-2C-C
2,5-dimethoxy-4-chloro
H
H
H
1538191-15-9
βk-2C-B
2,5-dimethoxy-4-bromo
H
H
H
807631-09-0
βk-2C-I
2,5-dimethoxy-4-iodo
H
H
H
βk-2C-D
2,5-dimethoxy-4-methyl
H
H
H
1368627-25-1
βk-2C-E
2,5-dimethoxy-4-ethyl
H
H
H
1517021-02-1
βk-2C-P
2,5-dimethoxy-4-propyl
H
H
H
βk-2C-iP
2,5-dimethoxy-4-isopropyl
H
H
H
1511033-62-7
βk-DOB
2,5-dimethoxy-4-bromo
Me
H
H
βk-MDOM
2,5-dimethoxy-4-methyl
Me
H
Me
βk-MDA
3,4-methylenedioxy
Me
H
H
80535-73-5
N-Acetyl-βk-MDA
3,4-methylenedioxy
Me
H
acetyl
2,3-MDMC
2,3-methylenedioxy
Me
H
Me
1427205-87-5
Methylone
3,4-methylenedioxy
Me
H
Me
186028-79-5
Dimethylone
3,4-methylenedioxy
Me
Me
Me
109367-07-9
N-Acetylmethylone
3,4-methylenedioxy
Me
acetyl
Me
N-Hydroxymethylone
3,4-methylenedioxy
Me
hydroxy
Me
Ethylone
3,4-methylenedioxy
Me
H
Et
1112937-64-0
Diethylone
3,4-methylenedioxy
Me
Et
Et
N-Acetylethylone
3,4-methylenedioxy
Me
acetyl
Et
N-Isopropyl-βk-MDA
3,4-methylenedioxy
Me
H
iPr
MDPT
3,4-methylenedioxy
Me
H
t-Bu
186028-84-2
Benzylone (BMDP)
3,4-methylenedioxy
Me
H
Bn
1823274-68-5
N-Cyclohexylmethylone
3,4-methylenedioxy
Me
H
cyclohexyl
3,4-EDMC
3,4-ethylenedioxy
Me
H
Me
30253-44-2
βk-IMP
3,4-trimethylene
Me
H
Me
100608-69-3
βk-IBP
3,4-trimethylene
Et
H
Et
βk-IVP
3,4-trimethylene
nPr
H
Et
3-Fluorobuphedrone
3-F
Et
H
Me
4-Fluorobuphedrone
4-F
Et
H
Me
1368599-12-5
4-Bromobuphedrone
4-Br
Et
H
Me
3-Methylbuphedrone
3-Me
Et
H
Me
1797911-07-9
4-Me-MABP
4-Me
Et
H
Me
1336911-98-8
4-Me-NEB
4-Me
Et
H
Et
18268-19-4
2-F-NEB
2-F
Et
H
Et
3F-NEB
3-F
Et
H
Et
4-F-NEB
4-F
Et
H
Et
4-Me-DMB
4-Me
Et
Me
Me
3,4-DMEB
3,4-dimethyl
Et
H
Et
4-Methoxybuphedrone
4-MeO
Et
H
Me
Butylone
3,4-methylenedioxy
Et
H
Me
802575-11-7
Eutylone
3,4-methylenedioxy
Et
H
Et
802855-66-9
βk-PBDB
3,4-methylenedioxy
Et
H
nPr
Bn-4-MeMABP
4-Me
Et
H
Bn
1445751-39-2
BMDB
3,4-methylenedioxy
Et
H
Bn
1445751-47-2
N-Cyclohexylbutylone
3,4-methylenedioxy
Et
H
cyclohexyl
βk-DMBDB
3,4-methylenedioxy
Et
Me
Me
802286-83-5
βk-MMDMA
3,4-methylenedioxy-5-MeO
Me
H
Me
2230716-98-8
βk-MMDMA-2
2-MeO-3,4-methylenedioxy
Me
H
Me
βk-DMMDA
2,5-diMeO-3,4-methylenedioxy
Me
H
H
5-Methylmethylone
3,4-methylenedioxy-5-Me
Me
H
Me
1364933-83-4
5-Methylethylone
3,4-methylenedioxy-5-Me
Me
H
Et
1364933-82-3
2-Methylbutylone
2-Me-3,4-methylenedioxy
Et
H
Me
1364933-86-7
5-Methylbutylone
3,4-methylenedioxy-5-Me
Et
H
Me
1354631-29-0
Pentylone
3,4-methylenedioxy
nPr
H
Me
698963-77-8
N-Ethylpentylone
3,4-methylenedioxy
nPr
H
Et
727641-67-0
N-propylpentylone
3,4-methylenedioxy
nPr
H
nPr
N-butylpentylone
3,4-methylenedioxy
nPr
H
nBu
2,3-Dipentylone
2,3-methylenedioxy
nPr
Me
Me
Dipentylone
3,4-methylenedioxy
nPr
Me
Me
17763-13-2
N,N-Diethylnorpentylone
3,4-methylenedioxy
nPr
Et
Et
Hexylone
3,4-methylenedioxy
nBu
H
Me
Isohexylone
3,4-methylenedioxy
iBu
H
Me
1157947-89-1
Isoheptylone
3,4-methylenedioxy
iPe
H
Me
N-Ethylhexylone
3,4-methylenedioxy
nBu
H
Et
27912-41-0
N-Ethylheptylone
3,4-methylenedioxy
nPe
H
Et
4-MEAP
4-Me
nPr
H
Et
746540-82-9
3,4-DMEP
3,4-dimethyl
nPr
H
Et
2-F-Pentedrone
2-F
nPr
H
Me
3-F-Pentedrone
3-F
nPr
H
Me
4-F-Pentedrone
4-F
nPr
H
Me
4-Cl-Pentedrone
4-Cl
nPr
H
Me
2167949-43-9
4-Methylpentedrone
4-Me
nPr
H
Me
1373918-61-6
DL-4662
3,4-dimethoxy
nPr
H
Et
1674389-55-9
4-F-iPr-norpentedrone
4-F
nPr
H
iPr
3-CBV
3-Cl
nPr
H
tBu
4-methylhexedrone
4-Me
nBu
H
Me
MEH
4-Me
nBu
H
Et
3F-NEH
3-F
nBu
H
Et
4-F-hexedrone
4-F
nBu
H
Me
4-F-octedrone
4-F
hexyl
H
Me
α-phenylmephedrone
4-Me
phenyl
H
Me
βk-Ephenidine
H
phenyl
H
Et
22312-16-9
BMAPN
β-naphthyl instead of phenyl
Me
H
Me
βk-Methiopropamine
thiophen-2-yl instead of phenyl
Me
H
Me
24065-17-6
5-Cl-bk-MPA
5-chlorothiophen-2-yl instead of phenyl
Me
H
Me
βk-5-MAPB
benzofuran-5-yl instead of phenyl
Me
H
Me
βk-6-MAPB
benzofuran-6-yl instead of phenyl
Me
H
Me
βk-5-IT
indol-5-yl instead of phenyl
Me
H
H
1369231-36-6
βk-5F-NM-AMT[ 39]
5-fluoroindol-3-yl instead of phenyl
Me
H
Me
α-Phthalimidopropiophenone
H
Me
phthalimido
19437-20-8
PPPO
H
Me
piperidinyl
PPBO
H
Et
piperidinyl
92728-82-0
FPPVO
4-F
nPr
piperidinyl
3,4-Pr-PipVP
3,4-trimethylene
nPr
piperidinyl
MDPV-azepane
3,4-methylenedioxy
nPr
azepane
Caccure 907
4-SCH3
α,α-di-Me
morpholinyl
α-PPP
H
Me
pyrrolidinyl
19134-50-0
α-PBP
H
Et
pyrrolidinyl
13415-54-8
α-PVP (O-2387)
H
nPr
pyrrolidinyl
14530-33-7
α-PHP
H
nBu
pyrrolidinyl
13415-86-6
α-PHiP
H
iBu
pyrrolidinyl
α-PEP (α-PHPP)
H
nPe
pyrrolidinyl
13415-83-3
α-POP
H
hexyl
pyrrolidinyl
α-PNP
H
heptyl
pyrrolidinyl
DPPE (Alpha-D2PV )
H
phenyl
pyrrolidinyl
27590-61-0
α-PcPeP
H
cyclopentyl
pyrrolidinyl
α-PCYP
H
cyclohexyl
pyrrolidinyl
1803168-11-7
2-MePPP
2-Me
Me
pyrrolidinyl
2092429-83-7
3-MePPP
3-Me
Me
pyrrolidinyl
1214940-01-8
4-MePPP
4-Me
Me
pyrrolidinyl
1313393-58-6
3-MeO-PPP
3-MeO
Me
pyrrolidinyl
MOPPP
4-MeO
Me
pyrrolidinyl
478243-09-3
3-F-PPP
3-F
Me
pyrrolidinyl
1214939-99-7
FPPP
4-F
Me
pyrrolidinyl
28117-76-2
Cl-PPP
4-Cl
Me
pyrrolidinyl
93307-24-5
3-Br-PPP
3-Br
Me
pyrrolidinyl
Br-PPP
4-Br
Me
pyrrolidinyl
2,3-DMPPP
2,3-dimethyl
Me
pyrrolidinyl
2,4-DMPPP
2,4-dimethyl
Me
pyrrolidinyl
3,4-DMPPP
3,4-dimethyl
Me
pyrrolidinyl
3-MPBP
3-Me
Et
pyrrolidinyl
1373918-60-5
3-F-PBP
3-F
Et
pyrrolidinyl
1373918-59-2
MPBP
4-Me
Et
pyrrolidinyl
732180-91-5
FPBP
4-F
Et
pyrrolidinyl
1373918-67-2
EPBP
4-Et
Et
pyrrolidinyl
MOPBP
4-MeO
Et
pyrrolidinyl
MMOPBP
3-Me-4-MeO
Et
pyrrolidinyl
O-2384
3,4-dichloro
Et
pyrrolidinyl
850352-65-7
2-Me-PVP
2-Me
nPr
pyrrolidinyl
850352-54-4
3-Me-PVP
3-Me
nPr
pyrrolidinyl
13415-85-5
Pyrovalerone (O-2371)
4-Me
nPr
pyrrolidinyl
3563-49-3
4-Et-PVP
4-Et
nPr
pyrrolidinyl
3F-PVP
3-F
nPr
pyrrolidinyl
2725852-55-9
FPVP
4-F
nPr
pyrrolidinyl
850352-31-7
2-Cl-PVP
2-Cl
nPr
pyrrolidinyl
3-Cl-PVP
3-Cl
nPr
pyrrolidinyl
4-Cl-PVP
4-Cl
nPr
pyrrolidinyl
5537-17-7
3-Br-PVP
3-Br
nPr
pyrrolidinyl
4-Br-PVP
4-Br
nPr
pyrrolidinyl
MOPVP
4-MeO
nPr
pyrrolidinyl
5537-19-9
DMOPVP
3,4-dimethoxy
nPr
pyrrolidinyl
850442-84-1
DMPVP
3,4-dimethyl
nPr
pyrrolidinyl
O-2390
3,4-dichloro
nPr
pyrrolidinyl
850352-61-3
MFPVP
3-methyl-4-fluoro
nPr
pyrrolidinyl
MPHP
4-Me
nBu
pyrrolidinyl
34138-58-4
3F-PHP
3-F
nBu
pyrrolidinyl
4F-PHP
4-F
nBu
pyrrolidinyl
2230706-09-7
4-Cl-PHP
4-Cl
nBu
pyrrolidinyl
2748592-29-0
DMOPHP
3,4-dimethoxy
nBu
pyrrolidinyl
MFPHP
3-Me-4-F
nBu
pyrrolidinyl
3F-PiHP
3-F
iBu
pyrrolidinyl
4F-PiHP
4-F
iBu
pyrrolidinyl
O-2394
4-Me
iBu
pyrrolidinyl
850352-51-1
MPEP
4-Me
pentyl
pyrrolidinyl
4F-PV8
4-F
pentyl
pyrrolidinyl
4-MeO-PV8
4-MeO
pentyl
pyrrolidinyl
MFPEP
3-Me-4-F
pentyl
pyrrolidinyl
MCPEP
3-Me-4-Cl
pentyl
pyrrolidinyl
4F-PV9
4-F
hexyl
pyrrolidinyl
4-MeO-PV9
4-MeO
hexyl
pyrrolidinyl
α-Phenylpyrovalerone
4-Me
phenyl
pyrrolidinyl
MDPPP
3,4-methylenedioxy
Me
pyrrolidinyl
783241-66-7
MDMPP
3,4-methylenedioxy
α,α-di-Me
pyrrolidinyl
MDPBP
3,4-methylenedioxy
Et
pyrrolidinyl
784985-33-7
MDPV
3,4-methylenedioxy
nPr
pyrrolidinyl
687603-66-3
2,3-MDPV
2,3-methylenedioxy
nPr
pyrrolidinyl
5-Me-MDPV
3,4-methylenedioxy-5-Me
nPr
pyrrolidinyl
6-Me-MDPV
2-Me-4,5-methylenedioxy
nPr
pyrrolidinyl
6-MeO-MDPV
2-MeO-4,5-methylenedioxy
nPr
pyrrolidinyl
Br-MeO-MDPV
2,3-methylenedioxy-4-MeO-5-Br
nPr
pyrrolidinyl
MDPiVP
3,4-methylenedioxy
iPr
pyrrolidinyl
MDPHP
3,4-methylenedioxy
nBu
pyrrolidinyl
776994-64-0
MDPHiP
3,4-methylenedioxy
iBu
pyrrolidinyl
MDPEP (MD-PV8)
3,4-methylenedioxy
pentyl
pyrrolidinyl
24646-39-7
MDPOP (MD-PV9)
3,4-methylenedioxy
hexyl
pyrrolidinyl
24646-40-0
3,4-EtPV
3,4-dimethylene
nPr
pyrrolidinyl
5-PPDi
3,4-trimethylene
Et
pyrrolidinyl
Indanyl-α-PVP
3,4-trimethylene
nPr
pyrrolidinyl
2748590-83-0
5-BPDi
3,4-trimethylene
nBu
pyrrolidinyl
IPPV
3,4-trimethylene
phenyl
pyrrolidinyl
TH-PBP
3,4-tetramethylene
Et
pyrrolidinyl
TH-PVP
3,4-tetramethylene
nPr
pyrrolidinyl
2304915-07-7
TH-PHP
3,4-tetramethylene
nBu
pyrrolidinyl
5-DBFPV
2,3-dihydrobenzofuran-5-yl instead of Ph
nPr
pyrrolidinyl
1620807-94-4
3-BF-PVP
benzofuran-3-yl instead of Ph
nPr
pyrrolidinyl
Naphyrone (O-2482)
β-naphthyl instead of phenyl
nPr
pyrrolidinyl
850352-53-3
α-Naphyrone
α-naphthyl instead of phenyl
nPr
pyrrolidinyl
α-PPT
thiophen-2-yl instead of phenyl
Me
pyrrolidinyl
α-PBT
thiophen-2-yl instead of phenyl
Et
pyrrolidinyl
α-PVT
thiophen-2-yl instead of phenyl
nPr
pyrrolidinyl
1400742-66-6
Legality
On 2 April 2010, the Advisory Council on the Misuse of Drugs in the UK announced that a broad structure-based ban of this entire class of compounds would be instituted, following extensive publicity around grey-market sales and recreational use of mephedrone , a common member of the family. This ban covers compounds with the aforementioned general structure, with 28 compounds specifically named.[ 40]
"Any compound (not being bupropion or a substance for the time being specified in paragraph 2.2) structurally derived from 2-amino-1-phenyl-1-propanone by modification in any of the following ways, that is to say,
(i) by substitution in the phenyl ring to any extent with alkyl, alkoxy, alkylenedioxy, haloalkyl or halide substituents, whether or not further substituted in the phenyl ring by one or more other univalent substituents;
(ii) by substitution at the 3-position with an alkyl substituent;
(iii) by substitution at the nitrogen atom with alkyl or dialkyl groups, or by inclusion of the nitrogen atom in a cyclic structure."
— ACMD, 2 April 2010
This text was added as an amendment to the Misuse of Drugs Act 1971 , to come into force on 16 April 2010.[ 41] Note that four of the above compounds (cathinone, methcathinone, diethylpropion and pyrovalerone) were already illegal in the UK at the time the ACMD report was issued. Two compounds were specifically excluded from the ban, these being bupropion because of its common use in medicine and relative lack of abuse potential, and naphyrone because its structure falls outside the generic definition and not enough evidence was yet available to justify a ban.
Naphyrone analogues were subsequently banned in July 2010 following a further review by the ACMD,[ 42] [ 43] along with a further broad based structure ban even more expansive than the last.[ 44] [ 45]
"Any compound structurally derived from 2–aminopropan–1–one by substitution at the 1-position with any monocyclic, or fused-polycyclic ring system (not being a phenyl ring or alkylenedioxyphenyl ring system), whether or not the compound is
further modified in any of the following ways, that is to say—
(i) by substitution in the ring system to any extent with alkyl, alkoxy, haloalkyl
or halide substituents, whether or not further substituted in the ring system by
one or more other univalent substituents;
(ii) by substitution at the 3–position with an alkyl substituent;
(iii) by substitution at the 2-amino nitrogen atom with alkyl or dialkyl groups, or
by inclusion of the 2-amino nitrogen atom in a cyclic structure".
— Home Office, 13 July 2010.
General chemical structure of substituted naphyrones, with R1 -R3 defined in text The substitutions in the general structure for naphyrone analogues subject to the ban may be described as follows:
Cyc = any monocyclic, or fused-polycyclic ring system (not being a phenyl ring or alkylenedioxyphenyl ring system), including analogues where the ring system is substituted to any extent with alkyl, alkoxy, haloalkyl or halide substituents, whether or not further substituted in the ring system by one or more other univalent substituents
R1 = hydrogen or any alkyl group
R2 = hydrogen, any alkyl group, or incorporation in a cyclic structure
R3 = hydrogen, any alkyl group, or incorporation in a cyclic structure
More new derivatives have however continued to appear, with the UK reporting more novel cathinone derivatives detected in 2010 than any other country in Europe, with most of them first identified after the generic ban had gone into effect and thus already being illegal despite never having been previously reported.[ 46]
In the United States, substituted cathinones are the psychoactive ingredients in "bath salts " which as of July 2011 were banned by at least 28 states, but not by the federal government.[ 47]
See also
References
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^ Paillet-Loilier M, Cesbron A, Le Boisselier R, Bourgine J, Debruyne D (2014). "Emerging drugs of abuse: current perspectives on substituted cathinones" . Substance Abuse and Rehabilitation . 5 : 37– 52. doi :10.2147/SAR.S37257 . PMC 4043811 . PMID 24966713 .
^ Simmons SJ, Leyrer-Jackson JM, Oliver CF, Hicks C, Muschamp JW, Rawls SM, Olive MF (October 2018). "DARK Classics in Chemical Neuroscience: Cathinone-Derived Psychostimulants" . ACS Chemical Neuroscience . 9 (10): 2379– 2394. doi :10.1021/acschemneuro.8b00147 . PMC 6197900 . PMID 29714473 .
^ Beck O, Bäckberg M, Signell P, Helander A (April 2018). "Intoxications in the STRIDA project involving a panorama of psychostimulant pyrovalerone derivatives, MDPV copycats" . Clinical Toxicology . 56 (4): 256– 263. doi :10.1080/15563650.2017.1370097 . PMID 28895757 . S2CID 3401681 .
^ Majchrzak M, Celiński R, Kuś P, Kowalska T, Sajewicz M (2018). "The newest cathinone derivatives as designer drugs: an analytical and toxicological review" . Forensic Toxicology . 36 (1): 33– 50. doi :10.1007/s11419-017-0385-6 . PMC 5754390 . PMID 29367861 .
^ Colzato LS, Ruiz MJ, van den Wildenberg WP, Hommel B (2011). "Khat use is associated with impaired working memory and cognitive flexibility" . PLOS ONE . 6 (6): e20602. Bibcode :2011PLoSO...620602C . doi :10.1371/journal.pone.0020602 . PMC 3115937 . PMID 21698275 .
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^ 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 .
^ Baumann MH, Ayestas MA, Partilla JS, Sink JR, Shulgin AT, Daley PF, Brandt SD, Rothman RB, Ruoho AE, Cozzi NV (April 2012). "The designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue" . Neuropsychopharmacology . 37 (5): 1192– 203. doi :10.1038/npp.2011.304 . PMC 3306880 . PMID 22169943 .
^ a b Kuropka P, Zawadzki M, Szpot P (May 2023). "A narrative review of the neuropharmacology of synthetic cathinones-Popular alternatives to classical drugs of abuse". Hum Psychopharmacol . 38 (3): e2866. doi :10.1002/hup.2866 . PMID 36866677 . Another feature that distinguishes [substituted cathinones (SCs)] from amphetamines is their negligible interaction with the trace amine associated receptor 1 (TAAR1). Activation of this receptor reduces the activity of dopaminergic neurones, thereby reducing psychostimulatory effects and addictive potential (Miller, 2011; Simmler et al., 2016). Amphetamines are potent agonists of this receptor, making them likely to self‐inhibit their stimulating effects. In contrast, SCs show negligible activity towards TAAR1 (Kolaczynska et al., 2021; Rickli et al., 2015; Simmler et al., 2014, 2016). [...] The lack of self‐regulation by TAAR1 may partly explain the higher addictive potential of SCs compared to amphetamines (Miller, 2011; Simmler et al., 2013).
^ a b Simmler LD, Buchy D, Chaboz S, Hoener MC, Liechti ME (April 2016). "In Vitro Characterization of Psychoactive Substances at Rat, Mouse, and Human Trace Amine-Associated Receptor 1". J Pharmacol Exp Ther . 357 (1): 134– 144. doi :10.1124/jpet.115.229765 . PMID 26791601 .
^ Simmler LD, Rickli A, Hoener MC, Liechti ME (April 2014). "Monoamine transporter and receptor interaction profiles of a new series of designer cathinones". Neuropharmacology . 79 : 152– 160. doi :10.1016/j.neuropharm.2013.11.008 . PMID 24275046 .
^ Pottie E, Cannaert A, Stove CP (October 2020). "In vitro structure-activity relationship determination of 30 psychedelic new psychoactive substances by means of β-arrestin 2 recruitment to the serotonin 2A receptor". Arch Toxicol . 94 (10): 3449– 3460. doi :10.1007/s00204-020-02836-w . PMID 32627074 .
^ Europol 2008 Annual Report on the implementation of Council Decision 2005/387/JHA
^ Europol 2009 Annual Report on the implementation of Council Decision 2005/387/JHA
^ Europol 2010 Annual Report on the implementation of Council Decision 2005/387/JHA
^ Europol 2011 Annual Report on the implementation of Council Decision 2005/387/JHA
^ Europol 2012 Annual Report on the implementation of Council Decision 2005/387/JHA
^ Europol 2013 Annual Report on the implementation of Council Decision 2005/387/JHA
^ Europol 2014 Annual Report on the implementation of Council Decision 2005/387/JHA
^ Europol 2015 Annual Report on the implementation of Council Decision 2005/387/JHA
^ Europol 2016 Annual Report on the implementation of Council Decision 2005/387/JHA
^ Europol 2017 Annual Report on the implementation of Council Decision 2005/387/JHA
^ European Monitoring Center for Drugs and Drug Addiction (December 2020). New psychoactive substances: global markets, glocal threats and the COVID-19 pandemic. An update from the EU Early Warning System (PDF) . Luxembourg: Publications Office of the European Union. doi :10.2810/921262 . ISBN 9789294975584 .
^ Maurer HH, Kraemer T, Springer D, Staack RF (April 2004). "Chemistry, pharmacology, toxicology, and hepatic metabolism of designer drugs of the amphetamine (ecstasy), piperazine, and pyrrolidinophenone types: a synopsis". Therapeutic Drug Monitoring . 26 (2): 127– 31. doi :10.1097/00007691-200404000-00007 . PMID 15228152 . S2CID 9255084 .
^ Davis S, Rands-Trevor K, Boyd S, Edirisinghe M (April 2012). "The characterisation of two halogenated cathinone analogues: 3,5-difluoromethcathinone and 3,5-dichloromethcathinone". Forensic Science International . 217 (1– 3): 139– 45. doi :10.1016/j.forsciint.2011.10.042 . PMID 22088945 .
^ Liu C, Jia W, Li T, Hua Z, Qian Z (August 2017). "Identification and analytical characterization of nine synthetic cathinone derivatives N-ethylhexedrone, 4-Cl-pentedrone, 4-Cl-α-EAPP, propylone, N-ethylnorpentylone, 6-MeO-bk-MDMA, α-PiHP, 4-Cl-α-PHP, and 4-F-α-PHP". Drug Testing and Analysis . 9 (8): 1162– 1171. doi :10.1002/dta.2136 . PMID 27863142 .
^ Błażewicz A, Bednarek E, Popławska M, Olech N, Sitkowski J, Kozerski L (2019). "Identification and structural characterization of synthetic cathinones: N-propylcathinone, 2,4-dimethylmethcathinone, 2,4-dimethylethcathinone, 2,4-dimethyl-α-pyrrolidinopropiophenone, 4-bromo-α-pyrrolidinopropiophenone, 1-(2,3-dihydro-1H-inden-5-yl)-2-(pyrrolidin-1-yl)hexan-1-one and 2,4-dimethylisocathinone" . Forensic Toxicol . 37 (2): 288– 307. doi :10.1007/s11419-018-00463-w . S2CID 59618061 .
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α1
Agonists Antagonists
Abanoquil
Ajmalicine
Alfuzosin
Anisodamine
Anisodine
Atiprosin
Atypical antipsychotics (e.g., brexpiprazole , clozapine , olanzapine , quetiapine , risperidone )
Benoxathian
Beta blockers (e.g., adimolol , amosulalol , arotinolol , carvedilol , eugenodilol , labetalol )
Buflomedil
Bunazosin
Corynanthine
Dapiprazole
Domesticine
Doxazosin
Ergolines (e.g., acetergamine , ergotamine , dihydroergotamine , lisuride , nicergoline , terguride )
Etoperidone
Fenspiride
Hydroxyzine
Indoramin
Ketanserin
L-765,314
mCPP
Mepiprazole
Metazosin
Monatepil
Moxisylyte
Naftopidil
Nantenine
Neldazosin
Niaprazine
Niguldipine
Pardoprunox
Pelanserin
Perlapine
Phendioxan
Phenoxybenzamine
Phentolamine
Phenylpiperazine antidepressants (e.g., hydroxynefazodone , nefazodone , trazodone , triazoledione )
Piperoxan
Prazosin
Quinazosin
Quinidine
Silodosin
Spegatrine
Spiperone
Talipexole
Tamsulosin
Terazosin
Tiodazosin
Tolazoline
Tetracyclic antidepressants (e.g., amoxapine , maprotiline , mianserin )
Tricyclic antidepressants (e.g., amitriptyline , clomipramine , doxepin , imipramine , trimipramine )
Trimazosin
Typical antipsychotics (e.g., chlorpromazine , fluphenazine , loxapine , thioridazine )
Urapidil
WB-4101
Zolertine
α2
Agonists Antagonists
1-PP
Adimolol
Amesergide
Aptazapine
Atipamezole
Atypical antipsychotics (e.g., asenapine , brexpiprazole , clozapine , lurasidone , olanzapine , paliperidone , quetiapine , risperidone , zotepine )
Azapirones (e.g., buspirone , gepirone , ipsapirone , tandospirone )
BRL-44408
Buflomedil
Cirazoline
Efaroxan
Esmirtazapine
Fenmetozole
Fluparoxan
Idazoxan
Ketanserin
Lisuride
mCPP
Mianserin
Mirtazapine
NAN-190
Pardoprunox
Phentolamine
Phenoxybenzamine
Piperoxan
Piribedil
Rauwolscine
Rotigotine
Setiptiline
Spegatrine
Spiroxatrine
Sunepitron
Terguride
Tolazoline
Typical antipsychotics (e.g., chlorpromazine , fluphenazine , loxapine , thioridazine )
Yohimbine
β