3-Chloroamphetamine

3-Chloroamphetamine
Clinical data
Other names3-CA; meta-Chloroamphetamine; m-Chloroamphetamine; MCA; PAL-304; PAL304
Drug classPsychostimulant; Serotonergic neurotoxin
Identifiers
  • 1-(3-chlorophenyl)propan-2-amine
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC9H12ClN
Molar mass169.65 g·mol−1
3D model (JSmol)
  • CC(CC1=CC(=CC=C1)Cl)N
  • InChI=1S/C9H12ClN/c1-7(11)5-8-3-2-4-9(10)6-8/h2-4,6-7H,5,11H2,1H3
  • Key:ORWQJKNRYUIFJU-UHFFFAOYSA-N

3-Chloroamphetamine (3-CA; code name PAL-304), also known as meta-chloroamphetamine (MCA), is a psychostimulant of the amphetamine family and a serotonergic neurotoxin related to para-chloroamphetamine (PCA; 4-chloroamphetamine).[1][2][3][4]

The drug is a potent serotonin–norepinephrine–dopamine releasing agent (SNDRA).[5][6][7] Its EC50Tooltip half-maximal effective concentration values for induction of monoamine release are 9.4 nM for norepinephrine, 11.8 nM for dopamine, and 120 nM for serotonin. Hence, 3-CA shows around 10-fold preference for induction of catecholamine release over induction of serotonin release.[5][6][8][8][9]

3-CA is closely related to the potent serotonergic neurotoxin PCA.[10][11][1] In contrast to PCA, 3-CA produced no serotonergic neurotoxicity in rodents.[10][11][1] However, this was found to be due to rapid metabolism via para-hydroxylation.[11][1] When the metabolism of 3-CA was inhibited, the drug produced approximately equivalent serotonergic neurotoxicity to PCA.[11][1]

See also

References

  1. ^ a b c d e Biel JH, Bopp BA (1978). "Amphetamines: Structure-Activity Relationships". Stimulants. Boston, MA: Springer US. p. 1–39. doi:10.1007/978-1-4757-0510-2_1. ISBN 978-1-4757-0512-6. The position of the chloro substituent also markedly affects the activity of the compounds (Table 6). The effect of the meta derivative was approximately equivalent to that of the para derivative but only after inhibition of para-hydroxylation, while the ortho-substituted compound actually slightly raised rather than lowered the serotonin levels (Fuller and Molloy, 1974).
  2. ^ Coppola M, Mondola R (December 2013). "4-methylamphetamine (4-MA): chemistry, pharmacology and toxicology of a new potential recreational drug". Mini Reviews in Medicinal Chemistry. 13 (14): 2097–2101. doi:10.2174/13895575113136660106. PMID 24195663. [...] was less potent than amphetamine, 3-chloroamphetamine and 4-chloroamphetamine in inducing motor stimulation [31]. [...]
  3. ^ Lapoint J, Welker KL (2022). "Synthetic amphetamine derivatives, benzofurans, and benzodifurans". In Dargan P, Wood D (eds.). Novel Psychoactive Substances. Elsevier. pp. 247–278. doi:10.1016/b978-0-12-818788-3.00007-3. ISBN 978-0-12-818788-3. [...] amphetamine analogue required to increase motor activity by 200 percent was 38 μmol/kg for 4-MA, 16 μmol/kg for amphetamine and 24 μmol/kg for both 2- and 3-chloroamphetamine.
  4. ^ Fuller RW, Baker JC (November 1974). "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. doi:10.1111/j.2042-7158.1974.tb09206.x. PMID 4156568.
  5. ^ a b Forsyth AN (22 May 2012). "Synthesis and Biological Evaluation of Rigid Analogues of Methamphetamines". ScholarWorks@UNO. Retrieved 4 November 2024.
  6. ^ a b Blough B (July 2008). "Dopamine-releasing agents" (PDF). In Trudell ML, Izenwasser S (eds.). Dopamine Transporters: Chemistry, Biology and Pharmacology. Hoboken [NJ]: Wiley. pp. 305–320. ISBN 978-0-470-11790-3. OCLC 181862653. OL 18589888W.
  7. ^ Ross SB, Ogren SO, Renyi AL (October 1977). "Substituted amphetamine derivatives. I. Effect on uptake and release of biogenic monoamines and on monoamine oxidase in the mouse brain". Acta Pharmacol Toxicol (Copenh). 41 (4): 337–352. doi:10.1111/j.1600-0773.1977.tb02673.x. PMID 579062.
  8. ^ a b Blough BE, Landavazo A, Partilla JS, Baumann MH, Decker AM, Page KM, et al. (June 2014). "Hybrid dopamine uptake blocker-serotonin releaser ligands: a new twist on transporter-focused therapeutics". ACS Med Chem Lett. 5 (6): 623–627. doi:10.1021/ml500113s. PMC 4060932. PMID 24944732.
  9. ^ "Norfenfluramine to treat dravet syndrome". Google Patents. 9 March 2023. Retrieved 7 December 2024.
  10. ^ a b Fuller RW (May 1992). "Effects of p-chloroamphetamine on brain serotonin neurons". Neurochem Res. 17 (5): 449–456. doi:10.1007/BF00969891. PMID 1528354.
  11. ^ a b c d Fuller RW (June 1978). "Structure-activity relationships among the halogenated amphetamines". Ann N Y Acad Sci. 305 (1): 147–159. Bibcode:1978NYASA.305..147F. doi:10.1111/j.1749-6632.1978.tb31518.x. PMID 152079.
Stub icon

This drug article relating to the nervous system is a stub. You can help Wikipedia by expanding it.