para-Chloromethamphetamine (PCMA; 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). It has been found to decrease serotonin in rats. 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.
Another study on rats found that 4-chloromethamphetamine was more potent at inducing conditioned taste aversion than methamphetamine.
4-CMA produces the head-twitch response in rodents similarly to 4-CA. This effect of 4-CMA can be blocked by a serotonin reuptake inhibitor.
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.
Studies in the 1970s found that a single dose of 10 mg/1 kg 4-CMA resulted in a decreased level of serotonin 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). 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.
See also Substituted amphetamine 3-Chloromethamphetamine 4-Bromoamphetamine 4-Bromomethamphetamine 4-Fluoroamphetamine 4-Fluoromethamphetamine 4-Iodoamphetamine
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