para-Chloroamphetamine

*para*-Chloroamphetamine
Clinical data
Other names	PCA; pCA; p-Chloroamphetamine; 4-Chloroamphetamine; 4-CA; Ro 4-6614/001; NSC-287208; 4-Chloro-α-methylphenethylamine; 1-(4-Chlorophenyl)propan-2-amine
Routes of; administration	Oral
Drug class	Serotonin–norepinephrine–dopamine releasing agent; Serotonergic neurotoxin; Antidepressant; Stimulant
Legal status
Legal status	DE: NpSG (Industrial and scientific use only); UK: Class A;
Pharmacokinetic data
Duration of action	IMTooltip Intramuscular Injection: 3–7 hours
Identifiers
	IUPAC name 1-(4-Chlorophenyl)propan-2-amine;
CAS Number	64-12-0 ;
PubChem CID	3127;
IUPHAR/BPS	4592;
ChemSpider	3015 ;
UNII	897NVD4A52;
ChEMBL	ChEMBL358967 ;
CompTox Dashboard (EPA)	DTXSID90897229 ;
Chemical and physical data
Formula	C9H12ClN
Molar mass	169.65 g·mol−1
3D model (JSmol)	Interactive image;
	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 ;
	(verify)

para-Chloroamphetamine (PCA), also known as 4-chloroamphetamine (4-CA), is a serotonin–norepinephrine–dopamine releasing agent (SNDRA) and serotonergic neurotoxin of the amphetamine family.^[2]^[3]^[4]^[5] It is used in scientific research in the study of the serotonin system, as a serotonin releasing agent (SRA) at lower doses to produce serotonergic effects, and as a serotonergic neurotoxin at higher doses to produce long-lasting depletions of serotonin.^[3]^[4]

PCA has also been clinically studied as an appetite suppressant and antidepressant, but findings of neurotoxicity in animals discouraged further evaluation.^[6]^[1] It has also been encountered as a designer drug, although it never achieved popularity, again perhaps due to its neurotoxicity.^[7]^[6]

^ ^a ^b Shulgin AT (1978). "Psychotomimetic Drugs: Structure-Activity Relationships". In Iversen LL, Iversen SD, Snyder SH (eds.). Stimulants. Boston, MA: Springer US. pp. 243–333. doi:10.1007/978-1-4757-0510-2_6. ISBN 978-1-4757-0512-6. Considerable clinical application of 4-CA has been made, and it has been found effective as an antidepressant when used chronically at levels of 75 mg/day (van Praag et al., 1971; van Praag and Korf, 1976). There are very few side effects noted and the drug is tolerated very well. However, indications of raphe-nucleus degeneration (Yunger et al., 1974) and related neurotoxicity (Harvey and McMaster, 1976) in experimental animals have discouraged further clinical study. [...] There were no reports from the clinical studies of 4-CA that suggested any psychotomimetic action.
^ Shulgin A, Manning T, Daley PF (2011). The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds. Vol. 1. Berkeley: Transform Press. ISBN 978-0-9630096-3-0.
^ ^a ^b Cite error: The named reference Fuller1992 was invoked but never defined (see the help page).
^ ^a ^b Cite error: The named reference Fuller1986 was invoked but never defined (see the help page).
^ Cite error: The named reference Fuller1978 was invoked but never defined (see the help page).
^ ^a ^b 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 Sci Int. 288: 173–180. doi:10.1016/j.forsciint.2018.04.023. hdl:1854/LU-8569680. PMID 29753935. Psychoactive effects of 4-CMA and 4-CA were evaluated in humans while researching both compounds as antidepressants. In the dosages used (80-90 mg daily, in 3 doses), no significant acute psychoactive effects were noticed; adverse effects were also low, although an effect on sleep and nausea was mentioned [7].
^ Luethi D, Liechti ME (April 2020). "Designer drugs: mechanism of action and adverse effects". Arch Toxicol. 94 (4): 1085–1133. Bibcode:2020ArTox..94.1085L. doi:10.1007/s00204-020-02693-7. PMC 7225206. PMID 32249347. Compared with amphetamine, an increase in serotonergic toxicity has been reported for the para-chlorinated derivative 4-chloroamphetamine, likely explained by highly potent serotonergic activity coupled with considerably potent dopaminergic activity (Colado et al. 1993; Fuller 1992; Johnson et al. 1990; Luethi et al. 2019b; Miller et al. 1986). However, unlike other halogenated stimulants, such as 4-fluoroamphetamine, 4-chloroamphetamine never achieved popularity as a designer drug, possibly because of its well-documented neurotoxicity.

[Shulgin1978-1] Shulgin AT (1978). "Psychotomimetic Drugs: Structure-Activity Relationships". In Iversen LL, Iversen SD, Snyder SH (eds.). Stimulants. Boston, MA: Springer US. pp. 243–333. doi:10.1007/978-1-4757-0510-2_6. ISBN 978-1-4757-0512-6. Considerable clinical application of 4-CA has been made, and it has been found effective as an antidepressant when used chronically at levels of 75 mg/day (van Praag et al., 1971; van Praag and Korf, 1976). There are very few side effects noted and the drug is tolerated very well. However, indications of raphe-nucleus degeneration (Yunger et al., 1974) and related neurotoxicity (Harvey and McMaster, 1976) in experimental animals have discouraged further clinical study. [...] There were no reports from the clinical studies of 4-CA that suggested any psychotomimetic action.

[ShulginManningDaley2011-2] Shulgin A, Manning T, Daley PF (2011). The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds. Vol. 1. Berkeley: Transform Press. ISBN 978-0-9630096-3-0.

[Fuller1992-3] Cite error: The named reference Fuller1992 was invoked but never defined (see the help page).

[Fuller1986-4] Cite error: The named reference Fuller1986 was invoked but never defined (see the help page).

[Fuller1978-5] Cite error: The named reference Fuller1978 was invoked but never defined (see the help page).

[BlanckaertVanquekelbergheCoopman2018-6] 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 Sci Int. 288: 173–180. doi:10.1016/j.forsciint.2018.04.023. hdl:1854/LU-8569680. PMID 29753935. Psychoactive effects of 4-CMA and 4-CA were evaluated in humans while researching both compounds as antidepressants. In the dosages used (80-90 mg daily, in 3 doses), no significant acute psychoactive effects were noticed; adverse effects were also low, although an effect on sleep and nausea was mentioned [7].

[LuethiLiechti2020-7] Luethi D, Liechti ME (April 2020). "Designer drugs: mechanism of action and adverse effects". Arch Toxicol. 94 (4): 1085–1133. Bibcode:2020ArTox..94.1085L. doi:10.1007/s00204-020-02693-7. PMC 7225206. PMID 32249347. Compared with amphetamine, an increase in serotonergic toxicity has been reported for the para-chlorinated derivative 4-chloroamphetamine, likely explained by highly potent serotonergic activity coupled with considerably potent dopaminergic activity (Colado et al. 1993; Fuller 1992; Johnson et al. 1990; Luethi et al. 2019b; Miller et al. 1986). However, unlike other halogenated stimulants, such as 4-fluoroamphetamine, 4-chloroamphetamine never achieved popularity as a designer drug, possibly because of its well-documented neurotoxicity.

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