4-Methylamphetamine
Stimulant and anorectic drug of the amphetamine class
From Wikipedia, the free encyclopedia
4-Methylamphetamine (4-MA) or para-methylamphetamine, 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).
administrationOral, intranasal, injection,
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| Trade names | Aptrol |
| Other names | 4-MA; PAL-313; PAL313; p-TAP; Normephedrine |
| Routes of administration | Oral, intranasal, injection, |
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| Elimination half-life | 6–12 hours |
| Excretion | Urine |
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| Formula | C10H15N |
| Molar mass | 149.237 g·mol−1 |
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Pharmacology
Pharmacodynamics
In vitro, 4-methylamphetamine acts as a potent and well-balanced serotonin, norepinephrine, and dopamine releasing agent (SNDRA) with EC50 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 5HT2C 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]
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][4]
| Compound | NE | DA | 5-HT | Ref |
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| Dextroamphetamine | 6.6–10.2 | 5.8–24.8 | 698–1,765 | [5][6][7][8] |
| Dextromethamphetamine | 12.3–14.3 | 8.5–40.4 | 736–1,292 | [5][9][7][8] |
| 4-Methylamphetamine | 22.2 | 44.1 | 53.4 | [1][10][7] |
| 4-Methylmethamphetamine (mephedrine) | 66.9 | 41.3 | 67.4 | [11][12] |
| 4-Methylcathinone (normephedrone) | 100 | 220 | 210 | [13][14][15] |
| 4-Methylmethcathinone (mephedrone) | 58–62.7 | 49.1–51 | 118.3–122 | [9][6][16][17][18] |
| 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: [19][20] | ||||
Natural occurrence
4-Methylamphetamine occurs naturally as an alkaloid in Thymus quinquecostatus plants, although its content even in young leaves is quite low [21][22]. In addition to it, there are related amphetamine structures or phenylpropanoids[23].
Society and culture
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.[27] More recently it has been reported as a novel designer drug.