Page last updated: 2024-12-05

p-chloroamphetamine

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Description

p-Chloroamphetamine: Chlorinated analog of AMPHETAMINE. Potent neurotoxin that causes release and eventually depletion of serotonin in the CNS. It is used as a research tool. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID3127
CHEMBL ID358967
SCHEMBL ID267030
MeSH IDM0015724

Synonyms (56)

Synonym
NCI60_002354
benzeneethanamine, 4-chloro-alpha-methyl-, (+-)-
(+-)-4-chloroamphetamine
(+-)-p-chloro-alpha-methylphenethylamine
dl-chloramphetamine
(+-)-p-chloroamphetamine
(+-)-p-chloramphetamine
phenethylamine, p-chloro-alpha-methyl-, (+-)-
nsc-287208
p-chloroamphetamine
4-chloramphetamine
4-chloro-.alpha.-methylphenethylamine
benzeneethanamine, 4-chloro-.alpha.-methyl-
p-chloramphetamine
64-12-0
phenethylamine, p-chloro-.alpha.-methyl-
4-chloroamphetamine
nsc287208
.alpha.-methyl-p-chlorophenethylamine
para chloroamphetamine
alpha-methyl-p-chlorophenethylamine
4-chloro-alpha-methylphenethylamine
para-chloroamphetamine
ly-121860
phenethylamine, p-chloro-alpha-methyl-
p-chloroamphetamine (van)
nsc 287208
benzeneethanamine, 4-chloro-alpha-methyl-
CHEMBL358967 ,
AKOS000157927
1-(4-chlorophenyl)propan-2-amine
2-(4-chloro-phenyl)-1-methyl-ethylamine
bdbm50029100
1-(4-chlorophenyl)-2-propanamine
A837315
unii-897nvd4a52
897nvd4a52 ,
gtpl4592
AB01001884-01
SCHEMBL267030
4-chloro-a-methyl-benzeneethanamine
MB01958
benzeneethanamine, 4-chloro-a-methyl-
(+/-)-2-(4-chlorophenyl)-1-methylethylamine
J-503288
1-(p-chlorophenyl)-2-aminopropane
1-(4-chlorophenyl)-2-propanamine #
dl-p-chloroamphetamine
Q229944
(+/-)-4-chloroamphetamine
(+/-)-p-chloroamphetamine
(+/-)-pca
dl-chloroamphetamine
(+/-)-1-methyl-2-(4-chlorophenyl)ethylamine
N10873
DTXSID90897229

Research Excerpts

Toxicity

ExcerptReferenceRelevance
" The present study was designed to test whether the toxic effects of PCA in the brain are dependent on release of endogenous 5-HT and to identify which stores of 5-HT are involved."( The neurotoxic effects of p-chloroamphetamine in rat brain are blocked by prior depletion of serotonin.
Berger, UV; Grzanna, R; Molliver, ME, 1992
)
0.58
" The neurochemical and histological effects of PCA are very similar to those produced by a large dose of methylamphetamine (MA) in that both drugs are toxic to serotonergic nerve terminals and neuronal perikarya in the somatosensory cortex."( Endogenously produced 5,6-dihydroxytryptamine may mediate the neurotoxic effects of para-chloroamphetamine.
Axt, KJ; Commins, DL; Seiden, LS; Vosmer, G, 1987
)
0.27
" It is proposed that toxic environment-PCA interactions may result from altered cardiovascular and/or thermoregulatory processes, mediated by enhanced catecholaminergic activity."( Environmental determinants of parachloroamphetamine toxicity in rats.
Gallus, JA; Gault, FP; Nearchou, NI; Sewell, RG, 1982
)
0.26

Pharmacokinetics

ExcerptReferenceRelevance
" Fluvoxamine pharmacokinetics was described by a population three-compartment pharmacokinetic model."( Pharmacokinetic-pharmacodynamic modeling of the effect of fluvoxamine on p-chloroamphetamine-induced behavior.
Danhof, M; Freijer, J; Geldof, M; Megens, AA; van Beijsterveldt, L; Vermote, PC, 2007
)
0.57

Dosage Studied

ExcerptRelevanceReference
" Experiments were designed to determine the dose-response and time-course for the effect of PCA administered intravenously on PRA in conscious, unrestrained rats."( Prazosin unmasks a renin response to intravenous para-chloroamphetamine.
Alper, RH; Pergola, PE; Sippy, BD; Zink, MH, 1990
)
0.28
" Adult female monkeys dosed po with 5 or 10 mg/kg of MDMA twice/day for 4 consecutive days demonstrated no spontaneous behavioral changes or weight loss compared to controls, but forebrain 5-HT concentration was reduced by 80% 1 mon after dosing."( Behavioral and neurochemical effects of orally administered MDMA in the rodent and nonhuman primate.
Ali, SF; Bailey, JR; Holson, RR; Hong, JS; Kolta, MG; McMillan, DE; Paule, MG; Scallet, AC; Scalzo, FM; Slikker, W, 1989
)
0.28
" Treatment of reserpinized rats with pargyline, a non-selective inhibitor of monoamine oxidase, in order to increase cerebral 5-HT levels, shifts the PCA dose-response curve for inducing the 5-HT behavioural syndrome to the left."( 5-Hydroxytryptamine release in vivo from a cytoplasmic pool: studies on the 5-HT behavioural syndrome in reserpinized rats.
Kuhn, DM; Wolf, WA; Youdim, MB, 1985
)
0.27
" This selectivity for 5-HT uptake was maintained after oral dosing for 14 days."( Biochemical effects of the antidepressant paroxetine, a specific 5-hydroxytryptamine uptake inhibitor.
Johnson, AM; Nelson, DR; Thomas, DR, 1987
)
0.27
" Acute and repeated dosing of sertraline decreased serotonin content of whole blood."( Sertraline, 1S,4S-N-methyl-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthylamine, a new uptake inhibitor with selectivity for serotonin.
Browne, RG; Koe, BK; Weissman, A; Welch, WM, 1983
)
0.27
" Depletion of serotonin with p-chlorophenylalanine, p-chloroamphetamine and 5,7-dihydroxytryptamine did not affect the initial dose-response curve to the centrally injected barbiturate, but all treatments resulted in significant delays in tolerance development."( The role of cerebral serotonin in the development of tolerance to centrally administered phenobarbital.
Lyness, WH; Mycek, MJ, 1980
)
0.51
" The dose-response curve for this discrimination was orderly with an ED50 of about one-half of the training dose (0."( A neuropharmacological analysis of the discriminative stimulus properties of fenfluramine.
Appel, JB; White, FJ, 1981
)
0.26
" The dose-response profiles for BDNF to stimulate 5-HT sprouting and Trk signaling were remarkably similar, suggesting a physiological link between the two events; both responses were maximal at intermediate doses of BDNF but declined at higher doses ("inverted-U-shaped" dose-response curves)."( BDNF promotes the regenerative sprouting, but not survival, of injured serotonergic axons in the adult rat brain.
Altar, CA; Blue, ME; Kaplan, DR; Lyons, WE; Mamounas, LA; Tessarollo, L, 2000
)
0.31
" In the present study, we determined the effect of high-dose D-FEN or PCA, administered according to a "neurotoxic" dosing regimen, on the density of SERT sites using ligand binding methods and on SERT protein levels using Western blots."( High-dose fenfluramine administration decreases serotonin transporter binding, but not serotonin transporter protein levels, in rat forebrain.
Baumann, MH; Cadet, JL; Dersch, CM; Jayanthi, S; Prisinzano, T; Rice, KC; Rothman, RB; Wang, X, 2003
)
0.32
"In this study, mice were exposed to dosing regimens of 3,4-methylenedioxymethamphetamine (MDMA), methamphetamine (METH), or parachloroamphetamine (PCA) known to deplete the monoamine neurotransmitters dopamine and serotonin, and the effects of these dosing regimens on learning and memory were assessed."( 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.
Fantegrossi, WE; Finton, BJ; Galloway, MP; Howell, LL; Murnane, KS; Perrine, SA, 2012
)
0.38
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (3)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Phenylethanolamine N-methyltransferaseHomo sapiens (human)IC50 (µMol)300.00000.00302.505710.0000AID155325
Sodium-dependent noradrenaline transporter Homo sapiens (human)IC50 (µMol)0.20700.00081.541620.0000AID471667
Sodium-dependent dopamine transporter Homo sapiens (human)IC50 (µMol)0.42400.00071.841946.0000AID471668
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (32)

Processvia Protein(s)Taxonomy
methylationPhenylethanolamine N-methyltransferaseHomo sapiens (human)
epinephrine biosynthetic processPhenylethanolamine N-methyltransferaseHomo sapiens (human)
catecholamine biosynthetic processPhenylethanolamine N-methyltransferaseHomo sapiens (human)
monoamine transportSodium-dependent noradrenaline transporter Homo sapiens (human)
neurotransmitter transportSodium-dependent noradrenaline transporter Homo sapiens (human)
chemical synaptic transmissionSodium-dependent noradrenaline transporter Homo sapiens (human)
response to xenobiotic stimulusSodium-dependent noradrenaline transporter Homo sapiens (human)
response to painSodium-dependent noradrenaline transporter Homo sapiens (human)
norepinephrine uptakeSodium-dependent noradrenaline transporter Homo sapiens (human)
neuron cellular homeostasisSodium-dependent noradrenaline transporter Homo sapiens (human)
amino acid transportSodium-dependent noradrenaline transporter Homo sapiens (human)
norepinephrine transportSodium-dependent noradrenaline transporter Homo sapiens (human)
dopamine uptake involved in synaptic transmissionSodium-dependent noradrenaline transporter Homo sapiens (human)
sodium ion transmembrane transportSodium-dependent noradrenaline transporter Homo sapiens (human)
monoamine transportSodium-dependent dopamine transporter Homo sapiens (human)
neurotransmitter transportSodium-dependent dopamine transporter Homo sapiens (human)
lactationSodium-dependent dopamine transporter Homo sapiens (human)
sensory perception of smellSodium-dependent dopamine transporter Homo sapiens (human)
locomotory behaviorSodium-dependent dopamine transporter Homo sapiens (human)
response to xenobiotic stimulusSodium-dependent dopamine transporter Homo sapiens (human)
response to iron ionSodium-dependent dopamine transporter Homo sapiens (human)
dopamine transportSodium-dependent dopamine transporter Homo sapiens (human)
adenohypophysis developmentSodium-dependent dopamine transporter Homo sapiens (human)
response to nicotineSodium-dependent dopamine transporter Homo sapiens (human)
positive regulation of multicellular organism growthSodium-dependent dopamine transporter Homo sapiens (human)
regulation of dopamine metabolic processSodium-dependent dopamine transporter Homo sapiens (human)
response to cocaineSodium-dependent dopamine transporter Homo sapiens (human)
dopamine biosynthetic processSodium-dependent dopamine transporter Homo sapiens (human)
dopamine catabolic processSodium-dependent dopamine transporter Homo sapiens (human)
response to ethanolSodium-dependent dopamine transporter Homo sapiens (human)
cognitionSodium-dependent dopamine transporter Homo sapiens (human)
dopamine uptake involved in synaptic transmissionSodium-dependent dopamine transporter Homo sapiens (human)
response to cAMPSodium-dependent dopamine transporter Homo sapiens (human)
norepinephrine uptakeSodium-dependent dopamine transporter Homo sapiens (human)
prepulse inhibitionSodium-dependent dopamine transporter Homo sapiens (human)
dopamine uptakeSodium-dependent dopamine transporter Homo sapiens (human)
hyaloid vascular plexus regressionSodium-dependent dopamine transporter Homo sapiens (human)
amino acid transportSodium-dependent dopamine transporter Homo sapiens (human)
norepinephrine transportSodium-dependent dopamine transporter Homo sapiens (human)
sodium ion transmembrane transportSodium-dependent dopamine transporter Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (18)

Processvia Protein(s)Taxonomy
phenylethanolamine N-methyltransferase activityPhenylethanolamine N-methyltransferaseHomo sapiens (human)
protein bindingPhenylethanolamine N-methyltransferaseHomo sapiens (human)
actin bindingSodium-dependent noradrenaline transporter Homo sapiens (human)
neurotransmitter transmembrane transporter activitySodium-dependent noradrenaline transporter Homo sapiens (human)
neurotransmitter:sodium symporter activitySodium-dependent noradrenaline transporter Homo sapiens (human)
dopamine:sodium symporter activitySodium-dependent noradrenaline transporter Homo sapiens (human)
norepinephrine:sodium symporter activitySodium-dependent noradrenaline transporter Homo sapiens (human)
protein bindingSodium-dependent noradrenaline transporter Homo sapiens (human)
monoamine transmembrane transporter activitySodium-dependent noradrenaline transporter Homo sapiens (human)
alpha-tubulin bindingSodium-dependent noradrenaline transporter Homo sapiens (human)
metal ion bindingSodium-dependent noradrenaline transporter Homo sapiens (human)
beta-tubulin bindingSodium-dependent noradrenaline transporter Homo sapiens (human)
protease bindingSodium-dependent dopamine transporter Homo sapiens (human)
signaling receptor bindingSodium-dependent dopamine transporter Homo sapiens (human)
neurotransmitter transmembrane transporter activitySodium-dependent dopamine transporter Homo sapiens (human)
dopamine:sodium symporter activitySodium-dependent dopamine transporter Homo sapiens (human)
protein bindingSodium-dependent dopamine transporter Homo sapiens (human)
monoamine transmembrane transporter activitySodium-dependent dopamine transporter Homo sapiens (human)
dopamine bindingSodium-dependent dopamine transporter Homo sapiens (human)
amine bindingSodium-dependent dopamine transporter Homo sapiens (human)
protein-containing complex bindingSodium-dependent dopamine transporter Homo sapiens (human)
metal ion bindingSodium-dependent dopamine transporter Homo sapiens (human)
protein phosphatase 2A bindingSodium-dependent dopamine transporter Homo sapiens (human)
heterocyclic compound bindingSodium-dependent dopamine transporter Homo sapiens (human)
norepinephrine:sodium symporter activitySodium-dependent dopamine transporter Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (15)

Processvia Protein(s)Taxonomy
cytosolPhenylethanolamine N-methyltransferaseHomo sapiens (human)
cytosolPhenylethanolamine N-methyltransferaseHomo sapiens (human)
plasma membraneSodium-dependent noradrenaline transporter Homo sapiens (human)
cell surfaceSodium-dependent noradrenaline transporter Homo sapiens (human)
membraneSodium-dependent noradrenaline transporter Homo sapiens (human)
neuronal cell body membraneSodium-dependent noradrenaline transporter Homo sapiens (human)
presynaptic membraneSodium-dependent noradrenaline transporter Homo sapiens (human)
plasma membraneSodium-dependent noradrenaline transporter Homo sapiens (human)
axonSodium-dependent noradrenaline transporter Homo sapiens (human)
cytoplasmSodium-dependent dopamine transporter Homo sapiens (human)
plasma membraneSodium-dependent dopamine transporter Homo sapiens (human)
cell surfaceSodium-dependent dopamine transporter Homo sapiens (human)
membraneSodium-dependent dopamine transporter Homo sapiens (human)
axonSodium-dependent dopamine transporter Homo sapiens (human)
neuron projectionSodium-dependent dopamine transporter Homo sapiens (human)
neuronal cell bodySodium-dependent dopamine transporter Homo sapiens (human)
axon terminusSodium-dependent dopamine transporter Homo sapiens (human)
membrane raftSodium-dependent dopamine transporter Homo sapiens (human)
postsynaptic membraneSodium-dependent dopamine transporter Homo sapiens (human)
dopaminergic synapseSodium-dependent dopamine transporter Homo sapiens (human)
flotillin complexSodium-dependent dopamine transporter Homo sapiens (human)
axonSodium-dependent dopamine transporter Homo sapiens (human)
presynaptic membraneSodium-dependent dopamine transporter Homo sapiens (human)
plasma membraneSodium-dependent dopamine transporter Homo sapiens (human)
neuronal cell body membraneSodium-dependent dopamine transporter Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (11)

Assay IDTitleYearJournalArticle
AID471665Inhibition of [3H]5-HT uptake at SERT in rat brain synaptosome2009European journal of medicinal chemistry, Dec, Volume: 44, Issue:12
Synthesis and serotonin transporter activity of sulphur-substituted alpha-alkyl phenethylamines as a new class of anticancer agents.
AID734192Inhibition of UBR protein in rabbit reticulocyte lysates assessed as inhibition of Tyr-nsP4 substrate degradation at 2 mM by immunoblotting analysis in presence of bestatin2013Journal of medicinal chemistry, Mar-28, Volume: 56, Issue:6
Development and characterization of monomeric N-end rule inhibitors through in vitro model substrates.
AID734187Inhibition of UBR protein in rabbit reticulocyte lysates assessed as inhibition of Tyr-nsP4 substrate degradation by in vitro synthesis/degradation assay2013Journal of medicinal chemistry, Mar-28, Volume: 56, Issue:6
Development and characterization of monomeric N-end rule inhibitors through in vitro model substrates.
AID734189Inhibition of UBR protein in rabbit reticulocyte lysates assessed as inhibition of Arg-nsP4 substrate degradation at 1 mM after 30 mins by Western blot analysis2013Journal of medicinal chemistry, Mar-28, Volume: 56, Issue:6
Development and characterization of monomeric N-end rule inhibitors through in vitro model substrates.
AID1136504Inhibition of PNMT in rabbit adrenal gland using norepinephrine as substrate1977Journal of medicinal chemistry, Apr, Volume: 20, Issue:4
A manual method for applying the Hansch approach to drug design.
AID471668Inhibition of human dopamine transporter2009European journal of medicinal chemistry, Dec, Volume: 44, Issue:12
Synthesis and serotonin transporter activity of sulphur-substituted alpha-alkyl phenethylamines as a new class of anticancer agents.
AID734188Inhibition of UBR protein in rabbit reticulocyte lysates assessed as inhibition of Arg-nsP4 substrate degradation by in vitro synthesis/degradation assay2013Journal of medicinal chemistry, Mar-28, Volume: 56, Issue:6
Development and characterization of monomeric N-end rule inhibitors through in vitro model substrates.
AID471667Inhibition of human noradrenaline transporter2009European journal of medicinal chemistry, Dec, Volume: 44, Issue:12
Synthesis and serotonin transporter activity of sulphur-substituted alpha-alkyl phenethylamines as a new class of anticancer agents.
AID734186Inhibition of UBR protein in rabbit reticulocyte lysates assessed as inhibition of Tyr-nsP4 substrate degradation measuring substrate half life at 2 mM2013Journal of medicinal chemistry, Mar-28, Volume: 56, Issue:6
Development and characterization of monomeric N-end rule inhibitors through in vitro model substrates.
AID155325In vitro inhibitory potency was measured against phenylethanolamine N-methyl-transferase1980Journal of medicinal chemistry, May, Volume: 23, Issue:5
Inhibitors of phenylethanolamine N-methyltransferase and epinephrine biosynthesis. 1. Chloro-substituted 1,2,3,4-tetrahydroisoquinolines.
AID241440Inhibitory concentration against monoamine oxidase A in rat brain mitochondrial suspension2005Journal of medicinal chemistry, Apr-07, Volume: 48, Issue:7
Sulfur-substituted alpha-alkyl phenethylamines as selective and reversible MAO-A inhibitors: biological activities, CoMFA analysis, and active site modeling.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (638)

TimeframeStudies, This Drug (%)All Drugs %
pre-1990360 (56.43)18.7374
1990's148 (23.20)18.2507
2000's98 (15.36)29.6817
2010's28 (4.39)24.3611
2020's4 (0.63)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 31.42

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be moderate demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index31.42 (24.57)
Research Supply Index6.49 (2.92)
Research Growth Index4.13 (4.65)
Search Engine Demand Index47.56 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (31.42)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials0 (0.00%)5.53%
Reviews16 (2.44%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other640 (97.56%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]