Para-Chloromethamphetamine

Not to be confused with para-Chloroamphetamine.

para-Chloromethamphetamine (also known as 4-chloromethamphetamine and 4-CMA) is a stimulant that is the N-methyl derivative and prodrug of the neurotoxic drug para-chloroamphetamine (4-CA).^[1][2] It has been found to decrease serotonin in rats.^[3][4][5] Further investigation into the long-term effects of chloroamphetamines discovered that administration of 4-CMA caused a prolonged reduction in the levels of serotonin and the activity of tryptophan hydroxylase in the brain one month after injection of a single dose of the drug.^[6]

para-Chloromethamphetamine

Legal status
Legal status	DE: NpSG (Industrial and scientific use only) UK: Class B
Identifiers
IUPAC name 1-(4-Chlorophenyl)-N-methylpropan-2-amine
CAS Number	30572-91-9 Y
PubChem CID	3128
ChemSpider	3016
UNII	IXP5G5WMYA
CompTox Dashboard (EPA)	DTXSID00897230
Chemical and physical data
Formula	C10H14ClN
Molar mass	183.68 g·mol−1
3D model (JSmol)	Interactive image
SMILES ClC1=CC=C(C=C1)CC(C)NC
InChI InChI=1S/C10H14ClN/c1-8(12-2)7-9-3-5-10(11)6-4-9/h3-6,8,12H,7H2,1-2H3 Key:XXLWNLKEOWWHDC-UHFFFAOYSA-N

Another study on rats found that 4-chloromethamphetamine was more potent at inducing conditioned taste aversion than methamphetamine.^[7]

4-Chloromethamphetamine was further investigated in the 1960s along with 4-CA and it was noted that they differed from their parent amphetamine and methamphetamine substances by exhibiting only a slight central stimulant effect in both animals and humans and that they acted like antidepressants rather than stimulants.^{[8][9][10][11]}

Tablet containing 4-chloromethamphetamine, found in 2015 in Belgium.

Studies in the 1970s found that a single dose of 10 mg/1 kg 4-CMA resulted in a decreased level of 5-hydroxytryptamine in the brain for several weeks.^[12]

4-Chloromethamphetamine was identified outside of the laboratory for the first time at the Tomorrowland festival edition 2015, where a tablet was found in possession of a drug dealer (see picture).^[13] In the following year, tablets with 4–CMA were also found in Romania, Austria and Croatia. Fortuitously, and for unknown reasons, 4-CMA disappeared briefly from the European rave scene after the Spring of 2016. However, a 2019 study of participants of a dance music festival in Belgium reported detection of 4-CMA in pills (out of 178 analyzed samples only one was mostly 4-CMA, while in one other 4-CMA was a minor ingredient).^[14]

See also

• 3-Chloromethamphetamine
• 4-Bromoamphetamine
• 4-Fluoroamphetamine
• 4-Fluoromethamphetamine
• 4-Iodoamphetamine

References

1. Johnson MP, Conarty PF, Nichols DE (July 1991). "[3H]monoamine releasing and uptake inhibition properties of 3,4-methylenedioxymethamphetamine and p-chloroamphetamine analogues". European Journal of Pharmacology. 200 (1): 9–16. doi:10.1016/0014-2999(91)90659-E. PMID 1685125.
2. Fuller RW, Baker JC, Perry KW, Molloy BB (October 1975). "Comparison of 4-chloro-, 4-bromo- and 4-fluoroamphetamine in rats: drug levels in brain and effects on brain serotonin metabolism". Neuropharmacology. 14 (10): 739–746. doi:10.1016/0028-3908(75)90099-4. PMID 1196472. S2CID 9620299.
3. Murnane KS, Perrine SA, Finton BJ, Galloway MP, Howell LL, Fantegrossi WE (April 2012). "Effects of exposure to amphetamine derivatives on passive avoidance performance and the central levels of monoamines and their metabolites in mice: correlations between behavior and neurochemistry". Psychopharmacology. 220 (3): 495–508. doi:10.1007/s00213-011-2504-0. PMC 3289749. PMID 21993877.
4. Pletscher A, Burkard WP, Bruderer H, Gey KF (November 1963). "Decrease of cerebral 5-hydroxytryptamine and 5-hydroxyindolacetic acid by an arylalkylamine". Life Sciences. 2 (11): 828–833. doi:10.1016/0024-3205(63)90094-8. PMID 14078137.
5. Fuller RW, Hines CW, Mills J (April 1965). "Lowering of brain serotonin level by chloramphetamines". Biochemical Pharmacology. 14 (4): 483–488. doi:10.1016/0006-2952(65)90221-2. PMID 14322972.
6. Sanders-Bush E, Bushing JA, Sulser F (January 1975). "Long-term effects of p-chloroamphetamine and related drugs on central serotonergic mechanisms". The Journal of Pharmacology and Experimental Therapeutics. 192 (1): 33–41. PMID 1123726.
7. Booth DA, Pilcher CW, D'Mello GD, Stolerman IP (December 1977). "Comparative potencies of amphetamine, fenfluramine and related compounds in taste aversion experiments in rats". British Journal of Pharmacology. 61 (4): 669–677. doi:10.1111/j.1476-5381.1977.tb07560.x. PMC 1668069. PMID 597669.
8. van Praag HM, Korf J, van Woudenberg F, Kits TP (July 1968). "Influencing the human indoleamine metabolism by means of a chlorinated amphetamine derivative with antidepressive action (p-chloro-N-methylamphetamine)". Psychopharmacologia. 13 (2): 145–160. doi:10.1007/BF00404812. PMID 5678577. S2CID 30028917.
9. Kits TP, van Praag HM (1970). "A controlled study of the antidepressant effect of p-Chloro-N-methylamphetamine, a compound with a selective effect on the central 5-hydroxytryptamine metabolism". Acta Psychiatrica Scandinavica. 46 (4): 365–373. doi:10.1111/j.1600-0447.1970.tb02126.x. PMID 5502782. S2CID 2211532.
10. van Praag HM, Korf J, van Woudenberg F (December 1970). "Investigation into the possible influence of chlorinated amphetamine derivatives on 5-hydroxytryptamine synthesis in man". Psychopharmacologia. 18 (4): 412–420. doi:10.1007/BF00402767. PMID 4923523. S2CID 27509683.
11. van Praag HM, Schut T, Bosma E, van den Bergh R (March 1971). "A comparative study of the therapeutic effects of sone 4-chlorinated amphetamine derivatives in depressive patients". Psychopharmacologia. 20 (1): 66–76. doi:10.1007/BF00404060. PMID 5565748. S2CID 5581.
12. Long-term effects of p-chloroamphetamine and related drugs on central serotonergic mechanisms. 1975. Journal of Pharmacology and Experimental Therapeutics. 192/1, 33-41. E. Sanders-Bush, J.A. Bushing, F. Sulser.
13. Blanckaert P, Vanquekelberghe S, Coopman V, Risseeuw MD, Van Calenbergh S, Cordonnier J (July 2018). "Identification and characterization of 4-chloromethamphetamine (4-CMA) in seized ecstacy - a risk to public health". Forensic Science International. 288: 173–180. doi:10.1016/j.forsciint.2018.04.023. hdl:1854/LU-8569680. PMID 29753935. S2CID 21720366.
14. Lessons to be learned from toxicological analyses in intoxicated patients and seized materials at an electronic music dance festival. 2019. Forensic Sci Int. 299/174-9. P. Calle, K. Maudens, S. Lemoyne, S. Geerts, D. Van Sassenbroeck, P. Jensen, et al. doi: 10.1016/j.forsciint.2019.03.047.