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| Other names | 3-MMC Metaphedrone 3-Methyl-N-methylcathinone; 3,N-Dimethylcathinone; 3,N-Dimethyl-β-ketoamphetamine; 3,α,N-Trimethyl-β-ketophenethylamine |
| Routes of administration | Oral Insufflated (most common) Injected |
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| Pharmacokinetic data | |
| Bioavailability | Oral: 5–9%[2] |
| Protein binding | Low[2] |
| Eliminationhalf-life | 50 min (in pigs)[2] |
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| Chemical and physical data | |
| Formula | C11H15NO |
| Molar mass | 177.247 g·mol−1 |
| 3D model (JSmol) | |
| Melting point | 193.2 °C (379.8 °F) ± 0.2°C (hydrochloride salt) |
| Boiling point | 280.5 °C (536.9 °F) ± 23.0°C at 760 mm Hg |
| Solubility in water | Sparingly soluble in PBS; slightly soluble in ethanol, dimethyl sulfoxide, and dimethyl formamide.[3] mg/mL (20 °C) |
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3-Methylmethcathinone (3-MMC), also known asmetaphedrone,[4] is adesigner drug from thesubstituted cathinone family. 3-MMC is amonoamine transporter substrate (a substance acted upon by monoamine transporters in the brain) that potently releases and inhibits the reuptake ofdopamine andnorepinephrine, as well as displaying moderateserotonin releasing activity.[5][6]
3-Methylmethcathinone is astructural isomer ofmephedrone (4-methylmethcathinone), and as such is illegal viablanket bans in many countries that have banned mephedrone. However, 3-MMC has still appeared on the recreational drug market as an alternative to mephedrone, and was first identified being sold in Sweden in 2012.[7] Unlike some other synthetic cathinones, 3-MMC has been evaluated in at least one large mammal study.[2]
3-MMC was first encountered in Sweden in 2012;[8] it was created as a designer drug following the control in many countries of the related compoundmephedrone. It was sold as a research chemical, usually in powdered form. There is no known or reported medical use of 3-MMC; it is primarily used recreationally.
Side effects of 3-MMC includeincreased heart rate,increased blood pressure, anddecreased appetite.[9]
A total of 27 fatalities with at least some exposure to 3-MMC have been confirmed as of March 2022. Eighteen of the 27 reported fatalities involved multiple drugs of abuse, usuallyopioids and uppers ("speedballs").[10] Of the 13 cases that specified sex, 12 deaths were male and 1 death was female. Of the 7 males whose age was reported, the median age was 27. The fatalities see a wide range of blood concentrations, from 249 to 1600 ng/mL.[11] Theroute of administration in any of these fatalities is not clear.
Of the presumably nine monointoxication deaths involving only 3-MMC that have occurred, two monointoxication cases were reported in theNetherlands and one was reported inFrance. The death in France was determined to be anaccidental overdose. In addition, there has been 291 reported cases of non-fatal 3-MMC intoxications. 213 of these cases (75%) were reported in Poland alone, and 50 cases (17%) were reported in Sweden.
Thetoxicokinetics of 3-MMC are thought to be similar to those for mephedrone. The first human study conducted in 14 healthy human volunteers concluded that "...low to moderate doses of 3-MMC were well tolerated and safe and that potential health risks might only occur at high or excessive doses of 3-MMC."[12]
3-MMC potently inhibits the reuptake ofmonoamines in the human norepinephrine (NET) anddopamine (DAT) transporters. It also acts as a triple releasing agent of dopamine, serotonin, and norepinephrine, similar to many othercathinones. As a releasing agent, it is more selective for dopamine and especiallynorepinephrine, suggesting that it has strongeramphetamine-like stimulant properties compared tomephedrone orMDMA.[5]
3-MMC also binds to serotonin5-HT1A,5-HT2A,5-HT2C receptors andadrenergic α1A and α2A receptors.[13] It binds much more strongly to the adrenergic receptors than the serotonergic 5-HT receptors, although it still retains significant serotonin-releasing activity (292 nM in one study). Other receptor interaction data have also been reported.[14] In contrast to mephedrone, 3-MMC is inactive as a serotonin 5-HT2A receptor agonist.[14]
3-MMC is inactive as anagonist of the rat and humanTAAR1 (EC50Tooltip half-maximal effective concentration = >10,000 nM).[15] Conversely, it is a low-potency weakpartial agonist of the mouse TAAR1 (EC50 = 3,800 nM,EmaxTooltip maximal efficacy = 25%).[15]
| Transporter | EC50 [nM][16] | IC50 [nM] |
|---|---|---|
| SERTTooltip Serotonin transporter | 292 | 4500 |
| NETTooltip Norepinephrine transporter | 27 | 80 |
| DATTooltip Dopamine transporter | 70 | 270 |
The oralbioavailability of 3-methylmethcathinone was determined at 7%[2] in one pig study, with peak blood concentrations (Tmax) attained within 5 to 10 minutes, and a relatively shorthalf-life of 50 minutes. Concentration inblood plasma dropped below detectability 24 hours after oral ingestion. Decreased feeding behavior resulted in weight loss for some.
Themetabolism of 3-MMC is not well-described. Knownmetabolites include 3-methylephedrine and 3-methylnorephedrine. A possible metabolic pathway is β-keto-reduction followed byN-demethylation.[17]
3-Methylmethcathinone's IUPAC name is 2-(methylamino)-1-(3-methylphenyl)propan-1-one). It is one of many synthetic cathinones,designer drugs related toamphetamines. It is astructural isomer ofmephedrone, and controlled as such. It can also be seen as the β-keto analog of3-methylmethamphetamine
3-MMC contains achiral center at the C-2 carbon. Therefore, twoenantiomers exist, the R and S enantiomer. It is assumed that the S form is morepotent due to its similarity to cathinone, but further research is needed to confirm this.[18]
There are several ways to synthesize 3-MMC. One route adapted from Power et al.[19] is to addethylmagnesium bromide to3-methylbenzaldehyde (I) to form the product1-(3-methylphenyl)-1-propanol (II). This product is then oxidized bypyridinium chlorochromate (PCC) onsilica gel to the ketone (III) and brominated withhydrobromic acid to yield the bromoketone (IV). This bromoketone is reacted with ethanolic methylamine to produce the 3-MMC free base (V), which can be converted to thehydrochloride salt (VI) by addition of ethereal hydrogen chloride (VI).[19]
As withmephedrone, users of 3-MMC typically report effects such as anelevated mood, pleasant body sensations, feelings oflove andempathy,euphoria, greater appreciation of music, heightenedlibido, and increasedconfidence and sociability.[20]
Adverse effects range from aggression,dry mouth, andjaw clenching, to more serious effects such ashyponatremia,seizures,hyperthermia andrhabdomyolysis.[20][8]
Due to its fleeting duration anddopaminergic effects, 3-MMC is highlyaddictive and commonly abused. Repeated dosing within a sitting is typical, sometimes using different routes, primarilyoral andintranasal. Common self-reported doses range from 50 to 150 mg, up to single 500 mg doses. Intranasal administration, or snorting, is the most commonroute of administration, followed by oral administration, followed by other routes, such as rectal administration andinjection into the bloodstream.
Users may dose repeatedly in order to extend the drugs duration, leading to 0.5—2 gram "sessions" that can span an evening. Single-dose effects last from 30 to 60 minutes, typically peaking around 10-minutes post-dose. In a questionnaire-based study of self-reported 3-MMC users inSlovenia, it was found that 88% of users insufflated the drug while 42% took it orally. The study did not find any instances of users injecting 3-MMC. Moreover, 26% of the users reported taking more than 1.5 grams of 3-MMC in a single sitting and over 50% reported having consumed more than 0.5 grams in a single sitting.[21]
3-Methylmethcathinone is commonly encountered as a white/off-white crystalline or pasty solid. It can be found sold in capsules. It is assumed to be aracemic mixture like mephedrone.
In the United States, 3-MMC is illegal as apositional isomer of thecontrolled substancemephedrone[22] It was explicitly designated as a controlled substance on 13 December 2023.[23]
Since October 2015, 3-MMC is acontrolled substance inChina.[24]
3-MMC is banned in theCzech Republic.[25]
3-MMC was not banned in 2016 by theUnited Nations Office on Drugs and Crime (UNODC) after a critical review.[26] However, following its subsequent abuse beginning in 2019, this decision was overturned and it was placed intoschedule II of the 1971 convention in March 2023.[1]
Effective 28 October 2021, 3-MMC has been scheduled under theDutch Opium Law and is therefore illegal in theNetherlands.[27]
3-MMC was given narcotic status inIndia on 8 February 2024.
3-MMC is under development for use as apharmaceutical drug in the potential treatment ofdyskinesias.[28] As of August 2023, it is inpreclinical research for this indication.[28] The drug is being developed by Clearmind Medicine.[28]
3-MMC is currently being developed as a medicine by the American biotech companyMindMed. They have filed for a patent to use 3-MMC for problems such associal anxiety disorder,post-traumatic stress disorder (PTSD), and as an adjunct incouples therapy.[29]
3-MMC is also undergoing clinical trials for its use in treating menstrual symptoms.[30] A successful trial has been completed in theUniversity of Maastricht. These efforts are led by the small Dutch company Period Pill.[31] The company has filed for patent coverage inCanada,Mexico,Croatia, theUnited States,Morocco,Japan,Brazil,Poland,Hungary, andKorea.
The first in-human clinical study of 3-MMC was published in December 2024.[9]
