4-Methylmethamphetamine

Not to be confused with Mephedrone, Meperidine, or Methedrine.

4-Methylmethamphetamine (4-MMA), also known as mephedrine, is a putative stimulant and entactogen drug of the amphetamine family. It acts as a serotonin–norepinephrine–dopamine releasing agent (SNDRA).^[1][2] The drug is the β-deketo analogue of mephedrone (4-methylmethcathinone; 4-MMC) and the N-methyl analogue of 4-methylamphetamine (4-MA).^[3][4]

4-Methylmethamphetamine

Clinical data
Other names	4-MMA; Mephedrine
Drug class	Stimulant; Serotonin–norepinephrine–dopamine releasing agent
ATC code	None
Legal status
Legal status	CA: Schedule I UK: Class A US: Schedule I (isomer of Etilamfetamime)
Identifiers
IUPAC name N-methyl-1-(4-methylphenyl)propan-2-amine
CAS Number	714965-56-7 Y hydrochloride: 161697-16-1 Y
PubChem CID	13803306
ChemSpider	23900071 Y
UNII	3R4PNL8UA7 hydrochloride: RN237JWQ2X Y
CompTox Dashboard (EPA)	DTXSID201024502
Chemical and physical data
Formula	C11H17N
Molar mass	163.264 g·mol−1
3D model (JSmol)	Interactive image
SMILES c1cc(C)ccc1CC(C)NC
InChI InChI=1S/C11H17N/c1-9-4-6-11(7-5-9)8-10(2)12-3/h4-7,10,12H,8H2,1-3H3 Y Key:GAIWFPOJOHUEBL-UHFFFAOYSA-N Y
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Pharmacology

Pharmacodynamics

4-MMA acts as a potent and well-balanced serotonin–norepinephrine–dopamine releasing agent (SNDRA).^[1][2] It induces hyperlocomotion and stereotypy (psychostimulant-like effects) as well as hyperthermia in mice, similarly to methcathinone.^[5][6]

Monoamine release of 4-methylmethamphetamine 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	[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. 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: [17][18]

Dopaminergic neurotoxicity

In contrast to methamphetamine and methcathinone, 4-MMA appears to produce minimal dopaminergic 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-keto substitutions on amphetamines may result in loss of activity at the vesicular monoamine transporter 2 (VMAT2), loss of elevations of cytosolic dopamine concentrations, and consequent loss of dopaminergic neurotoxic potential.^[5][6] Accordingly, the dopaminergic neurotoxicity of 4-MMA was greatly enhanced by the dopamine precursor levodopa (L-DOPA), the monoamine oxidase inhibitor (MAOI) pargyline, and methamphetamine (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]

See also

• 3-Methylmethamphetamine (3-MMA)
• 3-Methoxymethamphetamine (MMMA)
• 4-Methoxymethamphetamine (PMMA)
• 4-Fluoromethamphetamine (4-FMA)