Para-Chloromethamphetamine

Last updated

para-Chloromethamphetamine
4-CMA structure.png
Legal status
Legal status
  • DE: NpSG (Industrial and scientific use only)
  • UK: Class B
Identifiers
  • 1-(4-Chlorophenyl)-N-methylpropan-2-amine
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
Formula C10H14ClN
Molar mass 183.68 g·mol−1
3D model (JSmol)
  • ClC1=CC=C(C=C1)CC(C)NC
  • InChI=1S/C10H14ClN/c1-8(12-2)7-9-3-5-10(11)6-4-9/h3-6,8,12H,7H2,1-2H3
  • Key:XXLWNLKEOWWHDC-UHFFFAOYSA-N

para-Chloromethamphetamine (also known as 4-chloromethamphetamine and 4-CMA) is a stimulant that is the N-methyl derivative and prodrug of the neurotoxic drug para-chloroamphetamine (4-CA). [1] [2] It has been found to decrease serotonin in rats. [3] [4] [5] Further investigation into the long-term effects of chloroamphetamines discovered that administration of 4-CMA caused a prolonged reduction in the levels of serotonin and the activity of tryptophan hydroxylase in the brain one month after injection of a single dose of the drug. [6]

Another study on rats found that 4-chloromethamphetamine was more potent at inducing conditioned taste aversion than methamphetamine. [7]

4-Chloromethamphetamine was further investigated in the 1960s along with 4-CA and it was noted that they differed from their parent amphetamine and methamphetamine substances by exhibiting only a slight central stimulant effect in both animals and humans and that they acted like antidepressants rather than stimulants. [8] [9] [10] [11]

Tablet containing 4-chloromethamphetamine, found in 2015 in Belgium. Tablet containing 4-chloromethamphetamine.jpg
Tablet containing 4-chloromethamphetamine, found in 2015 in Belgium.

Studies in the 1970s found that a single dose of 10 mg/1 kg 4-CMA resulted in a decreased level of 5-hydroxytryptamine in the brain for several weeks. [12]

4-Chloromethamphetamine was identified outside of the laboratory for the first time at the Tomorrowland festival edition 2015, where a tablet was found in possession of a drug dealer (see picture). [13] In the following year, tablets with 4–CMA were also found in Romania, Austria and Croatia. Fortuitously, and for unknown reasons, 4-CMA disappeared briefly from the European rave scene after the Spring of 2016. However, a 2019 study of participants of a dance music festival in Belgium reported detection of 4-CMA in pills (out of 178 analyzed samples only one was mostly 4-CMA, while in one other 4-CMA was a minor ingredient). [14]

See also

Related Research Articles

α-Methyltryptamine Chemical compound

α-Methyltryptamine is a psychedelic, stimulant, and entactogen drug of the tryptamine family. It was originally developed as an antidepressant at Upjohn in the 1960s, and was used briefly as an antidepressant in the Soviet Union under the brand name Indopan or Indopane before being discontinued.

<span class="mw-page-title-main">4-Fluoroamphetamine</span> Psychoactive research chemical

4-Fluoroamphetamine, also known as para-fluoroamphetamine (PFA) is a psychoactive research chemical of the phenethylamine and substituted amphetamine chemical classes. It produces stimulant and entactogenic effects. As a recreational drug, 4-FA is sometimes sold along with related compounds such as 2-fluoroamphetamine and 4-fluoromethamphetamine.

<span class="mw-page-title-main">4-Methylthioamphetamine</span> Chemical compound

4-Methylthioamphetamine (4-MTA) is a designer drug of the substituted amphetamine class developed in the 1990s by a team led by David E. Nichols, an American pharmacologist and medical chemist, at Purdue University. It acts as a non-neurotoxic highly selective serotonin releasing agent (SSRA) in animals. 4-MTA is the methylthio derivative of amphetamine.

<span class="mw-page-title-main">4-Hydroxyamphetamine</span> Group of stereoisomers

Hydroxyamphetamine, also known as 4-hydroxyamphetamine or norpholedrine and sold under the brand names Paredrine and Paremyd among others, is a sympathomimetic medication used in eye drops to dilate the pupil for eye examinations.

<span class="mw-page-title-main">Chlorphentermine</span> Weight loss medication

Chlorphentermine, sold under the brand names Apsedon, Desopimon, and Lucofen, is a serotonergic appetite suppressant of the amphetamine family. Developed in 1962, it is the para-chloro derivative of the better-known appetite suppressant phentermine, which is still in current use.

<span class="mw-page-title-main">5-Fluoro-AMT</span> Chemical compound

5-Fluoro-α-methyltryptamine, also known as PAL-212 or PAL-544, is a putative stimulant, entactogen, and psychedelic tryptamine derivative related to α-methyltryptamine (αMT).

<i>para</i>-Chloroamphetamine Chemical compound

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. 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.

<span class="mw-page-title-main">MDAI</span> Chemical compound

MDAI, also known as 5,6-methylenedioxy-2-aminoindane, is an entactogen drug of the 2-aminoindane group which is related to MDMA and produces similar subjective effects.

<span class="mw-page-title-main">Amfonelic acid</span> Chemical compound

Amfonelic acid is a research chemical and dopaminergic stimulant with antibiotic properties. Limited clinical trials have been conducted, and it is primarily used in scientific research.

<span class="mw-page-title-main">MMAI</span> Chemical compound

5-Methoxy-6-methyl-2-aminoindane (MMAI) is a drug of the 2-aminoindane group developed in the 1990s by a team led by David E. Nichols at Purdue University. It acts as a less neurotoxic and highly selective serotonin releasing agent (SSRA) and produces entactogenic effects in humans. It has been sold as a designer drug and research chemical online since 2010.

<span class="mw-page-title-main">Serotonin releasing agent</span> Class of compounds

A serotonin releasing agent (SRA) is a type of drug that induces the release of serotonin into the neuronal synaptic cleft. A selective serotonin releasing agent (SSRA) is an SRA with less significant or no efficacy in producing neurotransmitter efflux at other types of monoamine neurons, including dopamine and norepinephrine neurons.

<span class="mw-page-title-main">Dopamine releasing agent</span> Type of drug

A dopamine releasing agent (DRA) is a type of drug which induces the release of dopamine in the body and/or brain.

<span class="mw-page-title-main">2-Aminotetralin</span> Chemical compound

2-Aminotetralin (2-AT), also known as 1,2,3,4-tetrahydronaphthalen-2-amine (THN), is a stimulant drug with a chemical structure consisting of a tetralin group combined with an amine.

<i>para</i>-Bromoamphetamine Chemical compound

para-Bromoamphetamine (PBA), also known as 4-bromoamphetamine (4-BA), is an amphetamine derivative which acts as a serotonin-norepinephrine-dopamine releasing agent (SNDRA) and produces stimulant effects.

<span class="mw-page-title-main">6-CAT</span> Chemical compound

6-Chloro-2-aminotetralin (6-CAT) is a drug which acts as a selective serotonin releasing agent (SSRA) and is a putative entactogen in humans. It is a rigid analogue of para-chloroamphetamine (PCA).

<span class="mw-page-title-main">4-Chlorophenylisobutylamine</span> Entactogen and stimulant drug of the phenethylamine class

4-Chlorophenylisobutylamine, also known as 4-chloro-α-ethylphenethylamine, is an entactogen and stimulant drug of the phenethylamine, amphetamine, and phenylisobutylamine families. It is an analogue of para-chloroamphetamine (PCA) where the alpha position methyl has been replaced with an ethyl group.

<span class="mw-page-title-main">5-Chloro-αMT</span> Chemical compound

5-Chloro-α-methyltryptamine (5-Chloro-αMT), also known as PAL-542, is a tryptamine derivative related to α-methyltryptamine (αMT) and one of only a few known specific serotonin-dopamine releasing agents (SDRAs). It has been investigated in animals as a potential treatment for cocaine dependence. The EC50 values of 5-chloro-αMT in evoking the in vitro release of serotonin (5-HT), dopamine (DA), and norepinephrine (NE) in rat synaptosomes were reported as 16 nM, 54 nM, and 3434 nM, with an NE/DA ratio of 63.6 and a DA/5-HT ratio of 3.38, indicating that it is a highly specific and well-balanced SDRA. However, 5-chloro-αMT has also been found to act as a potent full agonist of the 5-HT2A receptor, with an EC50 value of 6.27 nM and an efficacy of 105%. It is likely to act as a potent agonist of other serotonin receptors as well.

<span class="mw-page-title-main">3-Chloroamphetamine</span> Serotonergic neurotoxin

3-Chloroamphetamine (3-CA), also known as meta-chloroamphetamine, is a psychostimulant of the amphetamine family and a potent serotonergic neurotoxin related to para-chloroamphetamine (PCA). It is a potent serotonin–norepinephrine–dopamine releasing agent (SNDRA).

<span class="mw-page-title-main">2-Chloroamphetamine</span> Pharmaceutical compound

2-Chloroamphetamine (2-CA), also known as ortho-chloroamphetamine (OCA), is a monoamine releasing agent (MRA) of the amphetamine family related to 2-fluoroamphetamine (2-FA).

<i>para</i>-Bromomethamphetamine Pharmaceutical compound

para-Bromomethamphetamine, also known as 4-bromomethamphetamine (4-BMA), is a monoaminergic drug of the amphetamine family related to para-chloroamphetamine. It was studied by József Knoll and colleagues in the 1970s and 1980s.

References

  1. Johnson MP, Conarty PF, Nichols DE (July 1991). "[3H]monoamine releasing and uptake inhibition properties of 3,4-methylenedioxymethamphetamine and p-chloroamphetamine analogues". European Journal of Pharmacology. 200 (1): 9–16. doi:10.1016/0014-2999(91)90659-E. PMID   1685125.
  2. Fuller RW, Baker JC, Perry KW, Molloy BB (October 1975). "Comparison of 4-chloro-, 4-bromo- and 4-fluoroamphetamine in rats: drug levels in brain and effects on brain serotonin metabolism". Neuropharmacology. 14 (10): 739–746. doi:10.1016/0028-3908(75)90099-4. PMID   1196472. S2CID   9620299.
  3. Murnane KS, Perrine SA, Finton BJ, Galloway MP, Howell LL, Fantegrossi WE (April 2012). "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". Psychopharmacology. 220 (3): 495–508. doi:10.1007/s00213-011-2504-0. PMC   3289749 . PMID   21993877.
  4. Pletscher A, Burkard WP, Bruderer H, Gey KF (November 1963). "Decrease of cerebral 5-hydroxytryptamine and 5-hydroxyindolacetic acid by an arylalkylamine". Life Sciences. 2 (11): 828–833. doi:10.1016/0024-3205(63)90094-8. PMID   14078137.
  5. Fuller RW, Hines CW, Mills J (April 1965). "Lowering of brain serotonin level by chloramphetamines". Biochemical Pharmacology. 14 (4): 483–488. doi:10.1016/0006-2952(65)90221-2. PMID   14322972.
  6. Sanders-Bush E, Bushing JA, Sulser F (January 1975). "Long-term effects of p-chloroamphetamine and related drugs on central serotonergic mechanisms". The Journal of Pharmacology and Experimental Therapeutics. 192 (1): 33–41. PMID   1123726.
  7. Booth DA, Pilcher CW, D'Mello GD, Stolerman IP (December 1977). "Comparative potencies of amphetamine, fenfluramine and related compounds in taste aversion experiments in rats". British Journal of Pharmacology. 61 (4): 669–677. doi:10.1111/j.1476-5381.1977.tb07560.x. PMC   1668069 . PMID   597669.
  8. van Praag HM, Korf J, van Woudenberg F, Kits TP (July 1968). "Influencing the human indoleamine metabolism by means of a chlorinated amphetamine derivative with antidepressive action (p-chloro-N-methylamphetamine)". Psychopharmacologia. 13 (2): 145–160. doi:10.1007/BF00404812. PMID   5678577. S2CID   30028917.
  9. Kits TP, van Praag HM (1970). "A controlled study of the antidepressant effect of p-Chloro-N-methylamphetamine, a compound with a selective effect on the central 5-hydroxytryptamine metabolism". Acta Psychiatrica Scandinavica. 46 (4): 365–373. doi:10.1111/j.1600-0447.1970.tb02126.x. PMID   5502782. S2CID   2211532.
  10. van Praag HM, Korf J, van Woudenberg F (December 1970). "Investigation into the possible influence of chlorinated amphetamine derivatives on 5-hydroxytryptamine synthesis in man". Psychopharmacologia. 18 (4): 412–420. doi:10.1007/BF00402767. PMID   4923523. S2CID   27509683.
  11. van Praag HM, Schut T, Bosma E, van den Bergh R (March 1971). "A comparative study of the therapeutic effects of sone 4-chlorinated amphetamine derivatives in depressive patients". Psychopharmacologia. 20 (1): 66–76. doi:10.1007/BF00404060. PMID   5565748. S2CID   5581.
  12. Long-term effects of p-chloroamphetamine and related drugs on central serotonergic mechanisms. 1975. Journal of Pharmacology and Experimental Therapeutics. 192/1, 33-41. E. Sanders-Bush, J.A. Bushing, F. Sulser.
  13. 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 Science International. 288: 173–180. doi:10.1016/j.forsciint.2018.04.023. hdl: 1854/LU-8569680 . PMID   29753935. S2CID   21720366.
  14. Lessons to be learned from toxicological analyses in intoxicated patients and seized materials at an electronic music dance festival. 2019. Forensic Sci Int. 299/174-9. P. Calle, K. Maudens, S. Lemoyne, S. Geerts, D. Van Sassenbroeck, P. Jensen, et al. doi: 10.1016/j.forsciint.2019.03.047.