Para-Chloroamphetamine Explained

Para-Chloroamphetamine should not be confused with para-Chloromethamphetamine.

para-Chloroamphetamine (PCA), also known as 4-chloroamphetamine (4-CA), is a substituted amphetamine and monoamine releaser similar to MDMA, but with substantially higher neurotoxicity, thought to be due to the unrestrained release of both serotonin and dopamine by a metabolite.^[1] It is used as a neurotoxin by neurobiologists to selectively kill serotonergic neurons for research purposes, in the same way that 6-hydroxydopamine is used to kill dopaminergic neurons.^{[2] [3] [4] [5]}

para-Chloroamphetamine has been detected as an apparent designer drug,^[6] along with the related 3-chloroamphetamine, which is even more potent as a releaser of dopamine and serotonin but slightly less neurotoxic.^{[7] [8] [9] [10] [11]}

The closely related N-methylated derivative, para-chloromethamphetamine (CMA), which is metabolized to para-chloroamphetamine in vivo, has neurotoxic properties as well.

Legal status

China

As of October 2015, 4-CA is a controlled substance in China.^[12]

See also

• Substituted amphetamines
• para-Chloromethamphetamine (4-CMA)
• Chlorphentermine
• 3,4-Dichloroamphetamine (DCA)
• 4-Fluoroamphetamine (4-FA)
• 4-Methylamphetamine (4-MA)
• 5,7-Dihydroxytryptamine (5,7-DHT)
• para-Bromoamphetamine (PBA)
• para-Iodoamphetamine (PIA)

Notes and References

1. Miller KJ, Anderholm DC, Ames MM . Metabolic activation of the serotonergic neurotoxin para-chloroamphetamine to chemically reactive intermediates by hepatic and brain microsomal preparations . Biochemical Pharmacology . 35 . 10 . 1737–1742 . May 1986 . 3707603 . 10.1016/0006-2952(86)90332-1 .
2. Gal EM, Cristiansen PA, Yunger LM . Effect of p-chloroamphetamine on cerebral tryptophan-5-hydroxylase in vivo: a reexamination . Neuropharmacology . 14 . 1 . 31–39 . January 1975 . 125387 . 10.1016/0028-3908(75)90063-5 . 1068793 .
3. Curzon G, Fernando JC, Marsden CA . 5-Hydroxytryptamine: the effects of impaired synthesis on its metabolism and release in rat . British Journal of Pharmacology . 63 . 4 . 627–634 . August 1978 . 80243 . 1668117 . 10.1111/j.1476-5381.1978.tb17275.x .
4. Colado MI, Murray TK, Green AR . 5-HT loss in rat brain following 3,4-methylenedioxymethamphetamine (MDMA), p-chloroamphetamine and fenfluramine administration and effects of chlormethiazole and dizocilpine . British Journal of Pharmacology . 108 . 3 . 583–589 . March 1993 . 7682129 . 1908028 . 10.1111/j.1476-5381.1993.tb12846.x .
5. Freo U, Pietrini P, Pizzolato G, Furey M, Merico A, Ruggero S, Dam M, Battistin L . 6 . Cerebral metabolic responses to clomipramine are greatly reduced following pretreatment with the specific serotonin neurotoxin para-chloroamphetamine (PCA). A 2-deoxyglucose study in rats . Neuropsychopharmacology . 13 . 3 . 215–222 . November 1995 . 8602894 . 10.1016/0893-133X(95)00053-G . free .
6. Lin TC, Lin DL, Lua AC . Detection of p-chloroamphetamine in urine samples with mass spectrometry . Journal of Analytical Toxicology . 35 . 4 . 205–210 . May 2011 . 21513613 . 10.1093/anatox/35.4.205 . free .
7. Fuller RW, Schaffer RJ, Roush BW, Molloy BB . Drug disposition as a factor in the lowering of brain serotonin by chloroamphetamines in the rat . Biochemical Pharmacology . 21 . 10 . 1413–1417 . May 1972 . 5029422 . 10.1016/0006-2952(72)90365-6 .
8. Ogren SO, Ross SB . Substituted amphetamine derivatives. II. Behavioural effects in mice related to monoaminergic neurones . Acta Pharmacologica et Toxicologica . 41 . 4 . 353–368 . October 1977 . 303437 . 10.1111/j.1600-0773.1977.tb02674.x .
9. Ross SB, Kelder D . Inhibition of 3H-dopamine accumulation in reserpinized and normal rat striatum . Acta Pharmacologica et Toxicologica . 44 . 5 . 329–335 . May 1979 . 474143 . 10.1111/j.1600-0773.1979.tb02339.x .
10. Fuller RW, Baker JC . Long-lasting reduction of brain 5-hydroxytryptamine concentration by 3-chloramphetamine and 4-chloroamphetamine in iprindole-treated rats . The Journal of Pharmacy and Pharmacology . 26 . 11 . 912–914 . November 1974 . 4156568 . 10.1111/j.2042-7158.1974.tb09206.x . 41833796 .
11. Ross SB, Ogren SO, Renyi AL . Substituted amphetamine derivatives. I. Effect on uptake and release of biogenic monoamines and on monoamine oxidase in the mouse brain . Acta Pharmacologica et Toxicologica . 41 . 4 . 337–352 . October 1977 . 579062 . 10.1111/j.1600-0773.1977.tb02673.x .
12. Web site: 关于印发《非药用类麻醉药品和精神药品列管办法》的通知 . China Food and Drug Administration . 27 September 2015 . zh . 1 October 2015 . https://web.archive.org/web/20151001222554/http://www.sfda.gov.cn/WS01/CL0056/130753.html . 1 October 2015 . dead .