para-Chloroamphetamine

para-Chloroamphetamine

Systematic (IUPAC) name
1-(4-Chlorophenyl)propan-2-amine
Identifiers
CAS Number	64-12-0
PubChem	CID 3127
IUPHAR/BPS	4592
ChemSpider	3015
ChEMBL	CHEMBL358967
Chemical data
Formula	C9H12ClN
Molar mass	169.651 g/mol
SMILES Clc1ccc(cc1)CC(N)C
InChI InChI=1S/C9H12ClN/c1-7(11)6-8-2-4-9(10)5-3-8/h2-5,7H,6,11H2,1H3 Key:WWPITPSIWMXDPE-UHFFFAOYSA-N
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para-Chloroamphetamine (PCA), also known as 4-chloroamphetamine (4-CA), is an amphetamine derivative 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]

However, the effects of the compound on experimental animals appear less encouraging.^[6] It has been detected as an apparent designer drug,^[7] along with the related 3-chloroamphetamine, which is even more potent as a releaser of dopamine and serotonin but slightly less neurotoxic.^{[8][9][10][11][12]}

The closely related N-methylated derivative, para-Chloromethamphetamine (CMA), which is metabolised 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.^[13]

See also

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

References

1. Miller, K. J.; Anderholm, D. C.; Ames, M. M. (1986). "Metabolic activation of the serotonergic neurotoxin para-chloroamphetamine to chemically reactive intermediates by hepatic and brain microsomal preparations". Biochemical Pharmacology 35 (10): 1737–1742. doi:10.1016/0006-2952(86)90332-1. PMID 3707603.
2. Gal, E. M.; Cristiansen, P. A.; Yunger, L. M. (1975). "Effect of p-chloroamphetamine on cerebral tryptophan-5-hydroxylase in vivo: A reexamination". Neuropharmacology 14 (1): 31–9. doi:10.1016/0028-3908(75)90063-5. PMID 125387.
3. Curzon, G; Fernando, J. C.; Marsden, C. A. (1978). "5-Hydroxytryptamine: The effects of impaired synthesis on its metabolism and release in rat". British Journal of Pharmacology 63 (4): 627–34. doi:10.1111/j.1476-5381.1978.tb17275.x. PMC 1668117. PMID 80243.
4. Colado, M. I.; Murray, T. K.; Green, A. R. (1993). "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): 583–9. doi:10.1111/j.1476-5381.1993.tb12846.x. PMC 1908028. PMID 7682129.
5. Freo, U; Pietrini, P; Pizzolato, G; Furey, M; Merico, A; Ruggero, S; Dam, M; Battistin, L (1995). "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): 215–22. doi:10.1016/0893-133X(95)00053-G. PMID 8602894.
6. Alexander T. Shulgin (1978). Leslie L. Iversen, Susan D. Iversen, and Solomon H. Snyder, ed. Handbook of Psychopharmacology. 11: Stimulants. New York: Plenum Press.
7. Lin TC, Lin DL, Lua AC; Lin; Lua (2011). "Detection of p-chloroamphetamine in urine samples with mass spectrometry". Journal of Analytical Toxicology 35 (4): 205–210. doi:10.1093/anatox/35.4.205. PMID 21513613.
8. Fuller, R.; Schaffer, R. J.; Roush, B. W.; Molloy, B. B. (1972). "Drug disposition as a factor in the lowering of brain serotonin by chloroamphetamines in the rat". Biochemical Pharmacology 21 (10): 1413–1417. doi:10.1016/0006-2952(72)90365-6. PMID 5029422.
9. Ögren, S. O.; Ross, S. B. (2009). "Substituted Amphetamine Derivatives. II. Behavioural Effects in Mice Related to Monoaminergic Neurones". Acta Pharmacologica et Toxicologica 41 (4): 353–368. doi:10.1111/j.1600-0773.1977.tb02674.x. PMID 303437.
10. Ross, S. B.; Kelder, D. (2009). "Inhibition of 3H-Dopamine Accumulation in Reserpinized and Normal Rat Striatum". Acta Pharmacologica et Toxicologica 44 (5): 329–335. doi:10.1111/j.1600-0773.1979.tb02339.x. PMID 474143.
11. Fuller, R. W.; Baker, J. C. (1974). "Long-lasting reduction of brain 5-hydroxytryptamine concentration by 3-chloroamphetamine and 4-chloroamphetamine in iprindole-treated rats". Journal of Pharmacy and Pharmacology 26 (11): 912–914. doi:10.1111/j.2042-7158.1974.tb09206.x. PMID 4156568.
12. Ross, S. B.; Ögren, S. O.; Renyi, A. L. (2009). "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. doi:10.1111/j.1600-0773.1977.tb02673.x. PMID 579062.
13. "关于印发《非药用类麻醉药品和精神药品列管办法》的通知" (in Chinese). China Food and Drug Administration. 27 September 2015. Retrieved 1 October 2015.