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| Other names | 4-MMA; Mephedrine |
| Drug class | Stimulant;Serotonin–norepinephrine–dopamine releasing agent |
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| Formula | C11H17N |
| Molar mass | 163.264 g·mol−1 |
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4-Methylmethamphetamine (4-MMA), also known asmephedrine, is a putativestimulant andentactogendrug of theamphetamine family. It acts as aserotonin–norepinephrine–dopamine releasing agent (SNDRA).[1][2] The drug is theβ-deketoanalogue ofmephedrone (4-methylmethcathinone; 4-MMC) and theN-methyl analogue of4-methylamphetamine (4-MA).[3][4]
4-MMA acts as apotent and well-balancedserotonin–norepinephrine–dopamine releasing agent (SNDRA).[1][2] It induceshyperlocomotion andstereotypy (psychostimulant-like effects) as well ashyperthermia in mice, similarly tomethcathinone.[5][6]
| Compound | NETooltip Norepinephrine | DATooltip Dopamine | 5-HTTooltip Serotonin | Ref |
|---|---|---|---|---|
| Dextroamphetamine | 6.6–10.2 | 5.8–24.8 | 698–1,765 | [7][8][9][10] |
| Dextromethamphetamine | 12.3–14.3 | 8.5–40.4 | 736–1,292 | [7][11][9][10] |
| 4-Methylamphetamine | 22.2 | 44.1 | 53.4 | [12][13][9] |
| 4-Methylmethamphetamine (mephedrine) | 66.9 | 41.3 | 67.4 | [1][2] |
| 4-Methylethylamphetamine | 182 | 550 | 102 | [1] |
| 4-Methylpropylamphetamine | 752 | IA | 650 | [1] |
| 4-Methylbutylamphetamine | IA | IA | IA | [1] |
| 4-Methylmethcathinone (mephedrone) | 58–62.7 | 49.1–51 | 118.3–122 | [11][8][14][15][16] |
| Notes: The smaller the value, the more strongly the drug releases the neurotransmitter. Theassays were done in rat brainsynaptosomes and humanpotencies may be different. See alsoMonoamine releasing agent § Activity profiles for a larger table with more compounds.Refs:[17][18] | ||||
In contrast tomethamphetamine and methcathinone, 4-MMA appears to produce minimaldopaminergic neurotoxicity in mice.[5][6] Conversely, mephedrone shows no dopaminergic neurotoxicity at all in mice.[5][6] It was theorized that 4-methyl and β-ketosubstitutions on amphetamines may result in loss of activity at thevesicular monoamine transporter 2 (VMAT2), loss of elevations ofcytosolic dopamine concentrations, and consequent loss of dopaminergic neurotoxic potential.[5][6] Accordingly, the dopaminergic neurotoxicity of 4-MMA was greatly enhanced by thedopamine precursorlevodopa (L-DOPA), themonoamine oxidase inhibitor (MAOI)pargyline, andmethamphetamine (a VMAT2 inhibitor/reverser), all of which are known to increase the cytosolic pool of dopamine.[6] However, in contrast to 4-MMA, the dopaminergic neurotoxicity of methcathinone was enhanced only by levodopa and of mephedrone was enhanced only by methamphetamine.[6]
RESULTS. Methamphetamine and amphetamine potently released NE (IC50s = 14.3 and 7.0 nM) and DA (IC50s = 40.4 nM and 24.8 nM), and were much less potent releasers of 5-HT (IC50s = 740 nM and 1765 nM). Phentermine released all three biogenic amines with an order of potency NE (IC50 = 28.8 nM)> DA (IC50 = 262 nM)> 5-HT (IC50 = 2575 nM). Aminorex released NE (IC50 = 26.4 nM), DA (IC50 = 44.8 nM) and 5-HT (IC50 = 193 nM). Chlorphentermine was a very potent 5-HT releaser (IC50 = 18.2 nM), a weaker DA releaser (IC50 = 935 nM) and inactive in the NE release assay. Chlorphentermine was a moderate potency inhibitor of [3H]NE uptake (Ki = 451 nM). Diethylpropion, which is self-administered, was a weak DA uptake inhibitor (Ki = 15 µM) and NE uptake inhibitor (Ki = 18.1 µM) and essentially inactive in the other assays. Phendimetrazine, which is self-administered, was a weak DA uptake inhibitor (IC50 = 19 µM), a weak NE uptake inhibitor (8.3 µM) and essentially inactive in the other assays.
