para-Chloromethamphetamine

{{Short description|Chemical compound}}

{{cs1 config|name-list-style=vanc|display-authors=6}}

{{distinguish|para-Chloroamphetamine}}

{{DISPLAYTITLE:para-Chloromethamphetamine}}

{{Infobox drug

| drug_name = para-Chloromethamphetamine

| IUPAC_name = 1-(4-Chlorophenyl)-N-methylpropan-2-amine

| image = 4-CMA structure.png

| image_class = skin-invert-image

| width = 220

| tradename =

| routes_of_administration =

| legal_status =

| legal_DE = NpSG

| legal_UK = Class B

| CAS_number_Ref = {{cascite|correct|??}}

| CAS_number = 30572-91-9

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = IXP5G5WMYA

| ATC_suffix =

| PubChem = 3128

| ChemSpiderID = 3016

| synonyms = Ro 4-6861; PCMA; CMA; 4-Chloromethamphetamine; 4-CMA

| C=10 | H=14 | Cl=1 | N=1

| smiles = ClC1=CC=C(C=C1)CC(C)NC

| StdInChI = 1S/C10H14ClN/c1-8(12-2)7-9-3-5-10(11)6-4-9/h3-6,8,12H,7H2,1-2H3

| StdInChIKey = XXLWNLKEOWWHDC-UHFFFAOYSA-N

}}

para-Chloromethamphetamine (also known as 4-chloromethamphetamine and 4-CMA; code name Ro 4-6861) is a stimulant that is the N-methyl derivative and prodrug of the neurotoxic drug para-chloroamphetamine (4-CA).{{cite book | vauthors = Usdin E, Effron DH | title=Psychotropic Drugs and Related Compounds | publisher=National Institute of Mental Health | date=1972 | page= | url=https://books.google.com/books?id=0rq7AAAAIAAJ&pg=PA357}}{{cite journal | vauthors = Johnson MP, Conarty PF, Nichols DE | title = [3H]monoamine releasing and uptake inhibition properties of 3,4-methylenedioxymethamphetamine and p-chloroamphetamine analogues | journal = European Journal of Pharmacology | volume = 200 | issue = 1 | pages = 9–16 | date = July 1991 | pmid = 1685125 | doi = 10.1016/0014-2999(91)90659-E }}{{cite journal | vauthors = Fuller RW, Baker JC, Perry KW, Molloy BB | title = Comparison of 4-chloro-, 4-bromo- and 4-fluoroamphetamine in rats: drug levels in brain and effects on brain serotonin metabolism | journal = Neuropharmacology | volume = 14 | issue = 10 | pages = 739–746 | date = October 1975 | pmid = 1196472 | doi = 10.1016/0028-3908(75)90099-4 | s2cid = 9620299 }} It has been found to decrease serotonin in rats.{{cite journal | vauthors = Murnane KS, Perrine SA, Finton BJ, Galloway MP, Howell LL, Fantegrossi WE | title = 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 | journal = Psychopharmacology | volume = 220 | issue = 3 | pages = 495–508 | date = April 2012 | pmid = 21993877 | pmc = 3289749 | doi = 10.1007/s00213-011-2504-0 }}{{cite journal | vauthors = Pletscher A, Burkard WP, Bruderer H, Gey KF | title = Decrease of cerebral 5-hydroxytryptamine and 5-hydroxyindolacetic acid by an arylalkylamine | journal = Life Sciences | volume = 2 | issue = 11 | pages = 828–833 | date = November 1963 | pmid = 14078137 | doi = 10.1016/0024-3205(63)90094-8 }}{{cite journal | vauthors = Fuller RW, Hines CW, Mills J | title = Lowering of brain serotonin level by chloramphetamines | journal = Biochemical Pharmacology | volume = 14 | issue = 4 | pages = 483–488 | date = April 1965 | pmid = 14322972 | doi = 10.1016/0006-2952(65)90221-2 }} 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.{{cite journal | vauthors = Sanders-Bush E, Bushing JA, Sulser F | title = Long-term effects of p-chloroamphetamine and related drugs on central serotonergic mechanisms | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 192 | issue = 1 | pages = 33–41 | date = January 1975 | pmid = 1123726 | url = http://jpet.aspetjournals.org/content/192/1/33.short }}

Another study on rats found that 4-chloromethamphetamine was more potent at inducing conditioned taste aversion than methamphetamine.{{cite journal | vauthors = Booth DA, Pilcher CW, D'Mello GD, Stolerman IP | title = Comparative potencies of amphetamine, fenfluramine and related compounds in taste aversion experiments in rats | journal = British Journal of Pharmacology | volume = 61 | issue = 4 | pages = 669–677 | date = December 1977 | pmid = 597669 | pmc = 1668069 | doi = 10.1111/j.1476-5381.1977.tb07560.x }}

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.{{cite journal | vauthors = van Praag HM, Korf J, van Woudenberg F, Kits TP | title = Influencing the human indoleamine metabolism by means of a chlorinated amphetamine derivative with antidepressive action (p-chloro-N-methylamphetamine) | journal = Psychopharmacologia | volume = 13 | issue = 2 | pages = 145–160 | date = July 1968 | pmid = 5678577 | doi = 10.1007/BF00404812 | s2cid = 30028917 }}{{cite journal | vauthors = Kits TP, van Praag HM | title = A controlled study of the antidepressant effect of p-Chloro-N-methylamphetamine, a compound with a selective effect on the central 5-hydroxytryptamine metabolism | journal = Acta Psychiatrica Scandinavica | volume = 46 | issue = 4 | pages = 365–373 | year = 1970 | pmid = 5502782 | doi = 10.1111/j.1600-0447.1970.tb02126.x | s2cid = 2211532 }}{{cite journal | vauthors = van Praag HM, Korf J, van Woudenberg F | title = Investigation into the possible influence of chlorinated amphetamine derivatives on 5-hydroxytryptamine synthesis in man | journal = Psychopharmacologia | volume = 18 | issue = 4 | pages = 412–420 | date = December 1970 | pmid = 4923523 | doi = 10.1007/BF00402767 | s2cid = 27509683 }}{{cite journal | vauthors = van Praag HM, Schut T, Bosma E, van den Bergh R | title = A comparative study of the therapeutic effects of sone 4-chlorinated amphetamine derivatives in depressive patients | journal = Psychopharmacologia | volume = 20 | issue = 1 | pages = 66–76 | date = March 1971 | pmid = 5565748 | doi = 10.1007/BF00404060 | s2cid = 5581 }}

File:Tablet containing 4-chloromethamphetamine.jpg

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.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.

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).{{cite journal | vauthors = Blanckaert P, Vanquekelberghe S, Coopman V, Risseeuw MD, Van Calenbergh S, Cordonnier J | title = Identification and characterization of 4-chloromethamphetamine (4-CMA) in seized ecstacy - a risk to public health | journal = Forensic Science International | volume = 288 | pages = 173–180 | date = July 2018 | pmid = 29753935 | doi = 10.1016/j.forsciint.2018.04.023 | hdl-access = free | s2cid = 21720366 | hdl = 1854/LU-8569680 | url = https://biblio.ugent.be/publication/8569680 }} 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).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.