4-Chloromethcathinone

4-Chloromethcathinone
Legal status
Legal status	BR: Class F2 (Prohibited psychotropics); DE: Anlage I (Authorized scientific use only); UK: Class B; UN: Psychotropic Schedule II; Illegal in China and Sweden;
Identifiers
	IUPAC name 1-(4-chlorophenyl)-2-(methylamino)-1-propanone;
CAS Number	1225843-86-6;
PubChem CID	82100418;
ChemSpider	25630416;
UNII	PTAYYYZMMT;
KEGG	C22721;
CompTox Dashboard (EPA)	DTXSID201014163;
ECHA InfoCard	100.257.446
Chemical and physical data
Formula	C10H12ClNO
Molar mass	197.66 g·mol−1
3D model (JSmol)	Interactive image;
Melting point	198 °C (388 °F)
	SMILES ClC1=CC=C(C(C(C)NC)=O)C=C1;
	InChI InChI=1S/C10H12ClNO/c1-7(12-2)10(13)8-3-5-9(11)6-4-8/h3-7,12H,1-2H3; Key:UEJBEYOXRNGPEI-UHFFFAOYSA-N;

4-Chloromethcathinone (also known as 4-CMC and Clephedrone) is a stimulant drug of the cathinone class that has been sold online as a designer drug.^[1]^[2]

4-CMC produces similar effects to mephedrone, and has been sold as an alternative in countries where mephedrone was scheduled.

Adverse effects

Short-term

4-CMC produces similar side effects to mephedrone, including: increased blood pressure, tachycardia, hyperthermia, and anxiety.^[3]

Neurotoxicity

Its chemical structure closely resembles para-chloromethamphetamine, raising concerns about its potential to readily induce cell death of serotoninergic neurons. However, no neurotoxicity of this kind has been found, but studies involving mice do indicate that it is neurotoxic through other mechanisms. 4-CMC is cytotoxic and induces oxidative stress.^[4]

Pharmacology

Pharmacodynamics

Similar to mephedrone, 4-CMC mainly acts as a serotonin–norepinephrine–dopamine releasing agent (SNDRA), and partially as a serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI) with similar potency.^[3]

Effects of 4-CMC and mephedrone on neurotransmitter release^[3]
Drug	Release at DAT EC₅₀ (nM)	Release at NET EC₅₀ (nM)	Release at SERT EC₅₀ (nM)
Mephedrone	103 ± 16	83 ± 20	188 ± 22
4-CMC	91 ± 11	99 ± 18	169 ± 20

Effects of 4-CMC and mephedrone on inhibition of neurotransmitter uptake^[3]
Drug	Uptake Inhibition at DAT IC₅₀ (nM)	Uptake Inhibition at NET IC₅₀ (nM)	Uptake Inhibition at SERT IC₅₀ (nM)
Mephedrone	769 ± 106	319 ± 40	600 ± 99
4-CMC	1014 ± 78	559 ± 57	542 ± 38

Legality

Clephedrone is an Anlage I controlled drug in Germany.

Sweden's public health agency suggested classifying 4-Chloromethcathinone (klefedron) as illegal narcotic on June 1, 2015.^[5]

As of October 2015 4-CMC is a controlled substance in China.^[6]

4-CMC is considered a Schedule 1 substance in Virginia.^[7]

In December 2019, the UNODC announced scheduling recommendations placing 4-CMC into Schedule II.^[8]

References

^ Taschwer M, Weiß JA, Kunert O, Schmid MG (November 2014). "Analysis and characterization of the novel psychoactive drug 4-chloromethcathinone (clephedrone)". Forensic Science International. 244: e56–e59. doi:10.1016/j.forsciint.2014.09.007. PMID 25280452.
^ Klavž J, Gorenjak M, Marinšek M (August 2016). "Suicide attempt with a mix of synthetic cannabinoids and synthetic cathinones: Case report of non-fatal intoxication with AB-CHMINACA, AB-FUBINACA, alpha-PHP, alpha-PVP and 4-CMC". Forensic Science International. 265: 121–124. doi:10.1016/j.forsciint.2016.01.018. PMID 26890319.
^ ^a ^b ^c ^d Chojnacki MR, Thorndike EB, Partilla JS, Rice KC, Schindler CW, Baumann MH (June 2023). "Neurochemical and Cardiovascular Effects of 4-Chloro Ring-Substituted Synthetic Cathinones in Rats". The Journal of Pharmacology and Experimental Therapeutics. 385 (3): 162–170. doi:10.1124/jpet.122.001478. PMC 10201577. PMID 36669877.
^ Wojcieszak J, Kuczyńska K, Zawilska JB (August 2020). "Four Synthetic Cathinones: 3-Chloromethcathinone, 4-Chloromethcathinone, 4-Fluoro-α-Pyrrolidinopentiophenone, and 4-Methoxy-α-Pyrrolidinopentiophenone Produce Changes in the Spontaneous Locomotor Activity and Motor Performance in Mice with Varied Profiles". Neurotoxicity Research. 38 (2): 536–551. doi:10.1007/s12640-020-00227-8. PMC 7334283. PMID 32506339.
^ "23 nya ämnen kan klassas som narkotika eller hälsofarlig vara" [23 new substances can be classified as narcotic drugs or substances dangerous to health]. Folkhälsomyndigheten [The Public Health Authority] (in Swedish). 1 June 2015. Retrieved 5 September 2015.
^ "关于印发《非药用类麻醉药品和精神药品列管办法》的通知" [Notice on Issuing the Measures for the Listing and Control of Non-Medicinal Narcotic Drugs and Psychotropic Substances] (in Chinese). China Food and Drug Administration. 27 September 2015. Archived from the original on 1 October 2015. Retrieved 1 October 2015.
^ "18VAC110-20-322. Placement of Chemicals in Schedule I." Commonwealth of Virginia. 2 December 2015. Retrieved 11 March 2016.
^ "World Health Organization recommends 12 NPS for scheduling". WHO. December 2019.

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[1] Taschwer M, Weiß JA, Kunert O, Schmid MG (November 2014). "Analysis and characterization of the novel psychoactive drug 4-chloromethcathinone (clephedrone)". Forensic Science International. 244: e56–e59. doi:10.1016/j.forsciint.2014.09.007. PMID 25280452.

[2] Klavž J, Gorenjak M, Marinšek M (August 2016). "Suicide attempt with a mix of synthetic cannabinoids and synthetic cathinones: Case report of non-fatal intoxication with AB-CHMINACA, AB-FUBINACA, alpha-PHP, alpha-PVP and 4-CMC". Forensic Science International. 265: 121–124. doi:10.1016/j.forsciint.2016.01.018. PMID 26890319.

[:0-3] Chojnacki MR, Thorndike EB, Partilla JS, Rice KC, Schindler CW, Baumann MH (June 2023). "Neurochemical and Cardiovascular Effects of 4-Chloro Ring-Substituted Synthetic Cathinones in Rats". The Journal of Pharmacology and Experimental Therapeutics. 385 (3): 162–170. doi:10.1124/jpet.122.001478. PMC 10201577. PMID 36669877.

[pmid32506339-4] Wojcieszak J, Kuczyńska K, Zawilska JB (August 2020). "Four Synthetic Cathinones: 3-Chloromethcathinone, 4-Chloromethcathinone, 4-Fluoro-α-Pyrrolidinopentiophenone, and 4-Methoxy-α-Pyrrolidinopentiophenone Produce Changes in the Spontaneous Locomotor Activity and Motor Performance in Mice with Varied Profiles". Neurotoxicity Research. 38 (2): 536–551. doi:10.1007/s12640-020-00227-8. PMC 7334283. PMID 32506339.

[5] "23 nya ämnen kan klassas som narkotika eller hälsofarlig vara" [23 new substances can be classified as narcotic drugs or substances dangerous to health]. Folkhälsomyndigheten [The Public Health Authority] (in Swedish). 1 June 2015. Retrieved 5 September 2015.

[6] "关于印发《非药用类麻醉药品和精神药品列管办法》的通知" [Notice on Issuing the Measures for the Listing and Control of Non-Medicinal Narcotic Drugs and Psychotropic Substances] (in Chinese). China Food and Drug Administration. 27 September 2015. Archived from the original on 1 October 2015. Retrieved 1 October 2015.

[7] "18VAC110-20-322. Placement of Chemicals in Schedule I." Commonwealth of Virginia. 2 December 2015. Retrieved 11 March 2016.

[8] "World Health Organization recommends 12 NPS for scheduling". WHO. December 2019.

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