4-Methylamphetamine

4-Methylamphetamine

Systematic (IUPAC) name
1-(4-methylphenyl)propan-2-amine
Clinical data
Routes of administration	Oral, intranasal, injection
Legal status
Legal status	CA: Schedule I DE: Anlage II (Prohibited) UK: Class A
Pharmacokinetic data
Biological half-life	6-12 hours
Excretion	Urine
Identifiers
CAS Number	22683-78-9
ATC code	none
PubChem	CID 199116
ChemSpider	172349
ChEMBL	CHEMBL166183
Chemical data
Formula	C10H15N
Molar mass	149.23 g/mol
SMILES NC(Cc1ccc(cc1)C)C
InChI InChI=1S/C10H15N/c1-8-3-5-10(6-4-8)7-9(2)11/h3-6,9H,7,11H2,1-2H3 Key:ZDHZDWSHLNBTEB-UHFFFAOYSA-N
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4-Methylamphetamine (4-MA; PAL-313; Aptrol; p-TAP) is a stimulant and anorectic drug of the phenethylamine and amphetamine chemical classes.

In vitro, it acts as a potent and balanced serotonin, norepinephrine, and dopamine releasing agent with K_i affinity values of 53.4nM, 22.2nM, and 44.1nM at the serotonin, norepinephrine, and dopamine transporters, respectively.^[1] However, more recent in vivo studies that involved performing microdialysis on rats showed a different trend. These studies showed that 4-methylamphetamine is much more potent at elevating serotonin (~18 x baseline) relative to dopamine (~5 x baseline). The authors speculated that this is because 5-HT release dampens DA release through some mechanism. For example, it was suggested that a possible cause for this could be activation of 5HT_2C receptors since this is known to inhibit DA release. In addition there are alternative explanations such as 5-HT release then going on to encourage GABA release, which has an inhibitory effect on DA neurons.^[2]

4-MA was investigated as an appetite suppressant in 1952 and was even given a trade name, Aptrol, but development was apparently never completed.^[3] More recently it has been reported as a novel designer drug.

In animal studies, 4-MA was shown to have the lowest rate of self-administration out of a range of similar drugs tested (the others being 3-methylamphetamine, 4-fluoroamphetamine, and 3-fluoroamphetamine), likely as a result of having the highest potency for releasing serotonin relative to dopamine.^[4][5]

More than a dozen deaths have been reported throughout Europe in 2012-2013 after consumption of amphetamine ('speed') contaminated with 4-methylamphetamine.

Since 4-MA has little, if any, desirable psychoactive properties, researchers doubt the substance was sold as amphetamine on purpose. A contaminated precursor, after synthesis yielding a mixture of amphetamine and 4-MA, seems the logical culprit.^[6]

• 1-(4-Methylphenyl)-2-aminobutane
• 2-Methylamphetamine
• 3-Methylamphetamine
• 4-Methyl-N-methylamphetamine
• 4-Methyl-N-methylcathinone
• 3-Methoxy-4-methylamphetamine
• 3,4-Dimethylamphetamine

References

1. Wee, S.; Anderson, KG; Baumann, MH; Rothman, RB; Blough, BE; Woolverton, WL (2004). "Relationship between the Serotonergic Activity and Reinforcing Effects of a Series of Amphetamine Analogs". Journal of Pharmacology and Experimental Therapeutics 313 (2): 848–854. doi:10.1124/jpet.104.080101. PMID 15677348.
2. Di Giovanni, Giuseppe; Esposito, Ennio; Di Matteo, Vincenzo (2010). "Role of Serotonin in Central Dopamine Dysfunction". CNS Neuroscience & Therapeutics 16 (3): 179–194. doi:10.1111/j.1755-5949.2010.00135.x. PMID 20557570.
3. Gelvin, EP; McGavack, TH (1952). "2-Amino-1-(p-methylphenyl)-propane (aptrol) as an anorexigenic agent in weight reduction". New York state journal of medicine 52 (2): 223–6. PMID 14890975.
4. Wee, S; Anderson, KG; Baumann, MH; Rothman, RB; Blough, BE; Woolverton, WL (2005). "Relationship between the serotonergic activity and reinforcing effects of a series of amphetamine analogs.". The Journal of Pharmacology and Experimental Therapeutics 313 (2): 848–54. doi:10.1124/jpet.104.080101. PMID 15677348.
5. Baumann, MH; Clark, RD; Woolverton, WL; Wee, S; Blough, BE; Rothman, RB. (Apr 2011). "In vivo effects of amphetamine analogs reveal evidence for serotonergic inhibition of mesolimbic dopamine transmission in the rat". Journal of Pharmacology and Experimental Therapeutics 337 (1): 218–25. doi:10.1124/jpet.110.176271. PMC 3063744. PMID 21228061.
6. Blanckaert, P.; van Amsterdam, Jgc; Brunt, Tm; van den Berg, Jdj; Van Durme, F.; Maudens, K.; van Bussel, Jch (2013-09-01). "4-Methyl-amphetamine: a health threat for recreational amphetamine users". Journal of Psychopharmacology (Oxford, England) 27 (9): 817–822. doi:10.1177/0269881113487950. ISSN 1461-7285. PMID 23784740.