4-Methylamphetamine

4-Methylamphetamine (4-MA), also known by the former proposed brand name Aptrol, is a stimulant and anorectic drug of the amphetamine family. It is structurally related to mephedrone (4-methylmethcathinone).

4-Methylamphetamine

Clinical data
Trade names	Aptrol
Other names	4-MA; PAL-313; PAL313; p-TAP; Normephedrine
Routes of administration	Oral, intranasal, injection,
ATC code	none
Legal status
Legal status	CA: Schedule I DE: Anlage II (Authorized trade only, not prescriptible) UK: Class A US: Schedule II (isomer of Methamphetamine)
Pharmacokinetic data
Elimination half-life	6–12 hours
Excretion	Urine
Identifiers
IUPAC name 1-(4-methylphenyl)propan-2-amine
CAS Number	64-11-9 N
PubChem CID	199116
ChemSpider	172349 Y
UNII	9E273KL7HS
ChEMBL	ChEMBL166183 Y
CompTox Dashboard (EPA)	DTXSID50945351
Chemical and physical data
Formula	C10H15N
Molar mass	149.237 g·mol−1
3D model (JSmol)	Interactive image
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 Y Key:ZDHZDWSHLNBTEB-UHFFFAOYSA-N Y
NY (what is this?)  (verify)

Pharmacology

In vitro, 4-methylamphetamine acts as a potent and well-balanced serotonin, norepinephrine, and dopamine releasing agent (SNDRA) with EC₅₀Tooltip half-maximal effective concentration values of 53.4 nM, 22.2 nM, and 44.1 nM at the serotonin, norepinephrine, and dopamine transporters, respectively.^[1] Receptor interaction data for 4-methylamphetamine have also been reported.^[2]

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.^[3]

Monoamine release of 4-methylamphetamine and related agents (EC₅₀Tooltip Half maximal effective concentration, nM)

Compound	NETooltip Norepinephrine	DATooltip Dopamine	5-HTTooltip Serotonin	Ref
Dextroamphetamine	6.6–10.2	5.8–24.8	698–1,765	[4][5][6][7]
Dextromethamphetamine	12.3–14.3	8.5–40.4	736–1,292	[4][8][6][7]
4-Methylamphetamine	22.2	44.1	53.4	[1][9][6]
4-Methylmethamphetamine (mephedrine)	66.9	41.3	67.4	[10][11]
4-Methylcathinone (normephedrone)	100	220	210	[12][13][14]
4-Methylmethcathinone (mephedrone)	58–62.7	49.1–51	118.3–122	[8][5][15][16][17]
Notes: The smaller the value, the more strongly the drug releases the neurotransmitter. The assays were done in rat brain synaptosomes and human potencies may be different. See also Monoamine releasing agent § Activity profiles for a larger table with more compounds. Refs: [18][19]

Research

4-MA was investigated as an appetite suppressant in 1952 and was even given a trade name, Aptrol, but development was apparently never completed.^[20] 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.^[1][21]

Society and culture

More than a dozen deaths were reported throughout Europe in 2012-2013 after consumption of amphetamine ('speed') contaminated with 4-methylamphetamine.^[22][23][24]

See also

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