generation run 2026-04-21
180,698 min completedmodel pipeline-v5plan not recordedrun/ecfc3b18…Selection
Verification
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- seen / partial
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The model's own caveats
- sparse_evidence
Reproduce
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- 29 source keys (listed under Sources)
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- not recorded — template version, prompt hash and git SHA are written from 2026-09 onward
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- pipeline-v5
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- none — agent transcripts are persisted from 2026-09 onward
18 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | PubChem | 3-MMC | 1 | 1 | Primary chemical identity data for 3-MMC — confirms seed data formula/IUPAC name and provides missing InChIKey and MW |
| 2 | PubMed | 3-MMC 3-methylmethcathinone pharmacology | 15 | 15 | All 15 papers are directly relevant to 3-MMC pharmacology, safety, and clinical profile |
| 3 | OpenAlex | 3-methylmethcathinone 3-MMC synthetic cathinone | 345 | 4 | These foundational cathinone pharmacology papers provide class-level context for 3-MMC; will use selectively for mechanism of action where 3-MMC-specific data is absent |
| 4 | WebSearch | 3-MMC 3-methylmethcathinone legal status scheduling US UK EU Australia Canada 2024 | 10 | 2 | Jurisdictional legal status not well-covered in PubMed |
| 5 | PubMed | 3-methylmethcathinone monoamine transporter dopamine serotonin binding affinity | 1 | 1 | Key pharmacology paper characterizing mephedrone analogs at monoamine transporters |
| 6 | PubMed | structure-activity methcathinone analogs monoamine transporter | 1 | 1 | Provides key EC50 values for 3-MMC releasing potency at DAT (28 nM), NET (27 nM), SERT (268 nM) |
| 7 | WebSearch | WHO ECDD 3-MMC critical review 2022 pharmacology history synthesis first appearance | 10 | 1 | Critical WHO regulatory/pharmacological review document |
| 8 | OpenAlex | 3-MMC metaphedrone legal scheduling legislation | 3 | 1 | Important systematic review of 3-MMC prevalence and risks specifically in Netherlands context |
| 9 | PubMed · absence | 3-MMC pharmacokinetics plasma half-life Tmax bioavailability human | 0 | 0 | Gap noted - no standalone human PK study found |
| 10 | WHO ECDD | 3-MMC pharmacology, history, legal status | 1 | 0 | WHO critical review - source data for regulatory/pharmacological assessment |
| 11 | PMC/PubMed Central | 3-MMC pharmacological IC50 EC50 values DAT NET SERT | 1 | 1 | Primary quantitative pharmacological data for 3-MMC |
| 12 | PubChem + Cayman Chemical | 3-MMC CAS number SMILES synthesis | 1 | 2 | Chemical identity verification for brief seed data |
| 13 | WebSearch | 3-MMC metaphedrone monoamine transporter IC50 DAT NET SERT | 10 | 2 | Key pharmacological characterization data |
| 14 | WebSearch | 3-MMC tramadol lethal interaction case report death serotonin syndrome published | 10 | 0 | Gap identified - requires human review flag |
| 15 | EUDA/EMCDDA | 3-MMC risk assessment deaths seizures legal status | 1 | 3 | Official EU regulatory assessment with epidemiological data |
| 16 | OpenAlex | 3-MMC abuse potential reward self-administration reinforcing | 33 | 0 | Gap confirmed - no rodent self-administration model data published for 3-MMC specifically |
| 17 | WebSearch | 3-MMC LD50 animal study mouse rat toxic dose oral intravenous mg/kg | 10 | 0 | Gap confirmed for LD50 - needs flag in research output |
| 18 | WebSearch | 3-MMC Australia Canada scheduling legal status | 10 | 2 | Legal status for remaining key jurisdictions |
93 claims by section — every cited sentence, checked against its source
safety27 · 23 ok
Claim in safety — inconclusiveinconclusiveworking →
No specific antidote exists; management is supportive and extrapolated from cocaine/amphetamine toxidrome protocols.supported
No specific antidote; management extrapolated from cocaine/amphetamines. sar.s37257
The first published fatal case involved combined intoxication with approximately 500 mg 3-MMC, 400 mg 5-APB, and 80 g alcohol: the clinical course included agitation, seizures, hypertension, tachycardia, and hyperthermia, progressing to bradycardia and acute cardiovascular collapse within approximately 4 hourssupported
Patient administered ~500mg 3-MMC + 400mg 5-APB + 80g ethyl alcohol. Clinical manifestations: agitation, seizures, hypertension, tachycardia, hyperthermia, bradycardia. Death ~4h after drug use from acute cardiovascular collapse. j.forsciint.2014.10.016
A second case documented fatal 3-MMC poisoning in a 19-year-old female (blood concentration 800 ng/mL) without reported co-intoxicants.supported
Fatal case of suicide poisoning with 3-MMC. Blood concentration 800 ng/ml. j.forsciint.2019.02.040
In Italy, a significant epidemiological correlation has been identified between synthetic cathinone availability (including 3-MMC) and sudden unexpected deaths in youth (R² = 0.918, p = 2.63 × 10⁻⁷), though causality cannot be established from ecological datasupported
Exploratory correlation analysis of NPS availability (including 3-MMC) and sudden unexpected deaths/violence in youth in Italy/Europe. Strong correlations found (R²=0.918, p=2.63×10⁻⁷). s11739-025-04180-2
Dutch Poison Center data document a strong increase in NPS intoxications including 3-MMC among adolescents from 2014 to 2023.supported
Increasing trend in adolescent psychoactive substance intoxications reported to Dutch Poisons Information Center, including 3-MMC NPS. j.drugpo.2025.104860
3-MMC induces concentration-dependent hepatotoxicity in rat hepatocytes at human-relevant concentrations (24-hour exposure, 31 nM–10 mM)supported
3-MMC induces hepatotoxicity via oxidative stress, apoptosis, and autophagy in rat hepatocytes... at human-relevant concentrations. s00204-019-02539-x
Inhibition of CYP2D6 and CYP2E1 reduced toxicity, indicating that metabolic activation through these enzymes generates the hepatotoxic speciessupported
CYP2D6 and CYP2E1 are implicated in metabolism. s00204-019-02539-x
Chronic 3-MMC administration in rats reduced inhibitory synaptic transmission in the nucleus accumbens (decreased sIPSC amplitude) without affecting excitatory transmissionsupported
Decreased sIPSC amplitude in NAc after chronic exposure. fnmol.2022.975820
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
The biphasic anxiety pattern observed in rats — anxiolytic effects at acute dosing (3 mg/kg), anxiogenic effects after 7 days of chronic dosing — suggests that repeated use may produce or exacerbate anxiety disorders.supported
Acute 3 mg/kg produced anxiolytic effects; chronic 7-day dosing produced anxiety-like behavior. fnmol.2022.975820
A particularly concerning psychological risk is the compulsive redosing pattern documented across multiple contexts: recreational use, chemsex sessions, and clinical case reportssupported
higher craving/redosing/dependence potential than 4-MMC. Increasing treatment-seeking for problematic 3-MMC use. j.drugpo.2025.104971
A particularly concerning psychological risk is the compulsive redosing pattern documented across multiple contexts: recreational use, chemsex sessions, and clinical case reportssupported
Case report addressing addictive patterns of chemsex with 3-MMC. Discusses diagnostic criteria, predisposing factors, and treatment approaches for 3-MMC addiction. s13256-025-05492-9
The controlled trial did not assess tolerance development.supported
assessed the impact of three escalating doses of 3-MMC (25, 50 and 100 mg) on vital signs, neurocognitive function, state of consciousness, appetite and drug desire, in a cross-over, placebo-controlled trial. s41386-024-02042-7
Animal models: Conditioned place preference established at 3 and 10 mg/kg in rats (not at 1 mg/kg); CPP magnitude at 10 mg/kg comparable to methamphetamine at 3 mg/kg; VTA c-Fos activation exceeding methamphetaminepartially supported
3-MMC induced CPP at 3 or 10 mg/kg in rats... c-Fos activation in ACC, NAc, and VTA. fnmol.2022.975820
Clinical observation: Systematic review concluding 3-MMC produces "more craving, more frequent re-dosing, and more dependence than 4-MMC"; increasing treatment-seeking for 3-MMC dependence in the Netherlandssupported
higher craving/redosing/dependence potential than 4-MMC. Increasing treatment-seeking for problematic 3-MMC use. j.drugpo.2025.104971
Case reports: Documented 3-MMC addiction in chemsex context with discussion of diagnostic criteria for 3-MMC use disorder; multiple reports of compulsive sessional use with inability to self-limit dosingsupported
Case report addressing addictive patterns of chemsex with 3-MMC. Discusses diagnostic criteria, predisposing factors, and treatment approaches for 3-MMC addiction. s13256-025-05492-9
Case reports: Documented 3-MMC addiction in chemsex context with discussion of diagnostic criteria for 3-MMC use disorder; multiple reports of compulsive sessional use with inability to self-limit dosingpartially supported
31-year-old male intoxicated with 3-MMC (177 ng/mL blood) and GHB (131 mg/L) during slamsex session. Review of 13 chemsex/slamsex intoxication cases from literature. j.forsciint.2021.110743
Claim in safety — inconclusiveinconclusiveworking →
The most dangerous documented combination involved 3-MMC with 5-(2-aminopropyl)benzofuran (5-APB) and alcohol: approximately 500 mg 3-MMC combined with 400 mg of the serotonin-releasing benzofuran 5-APB and 80 g alcohol produced fatal cardiovascular collapse within 4 hourssupported
Patient administered ~500mg 3-MMC + 400mg 5-APB + 80g ethyl alcohol... Death ~4h after drug use from acute cardiovascular collapse. j.forsciint.2014.10.016
A non-fatal severe intoxication occurred during combined 3-MMC and GHB use in a chemsex context (blood 3-MMC 177 ng/mL, GHB 131 mg/L), presenting with severe impaired consciousnesssupported
31-year-old male intoxicated with 3-MMC (177 ng/mL blood) and GHB (131 mg/L) during slamsex session. j.forsciint.2021.110743
Multiple chemsex case reports document 3-MMC combined with GHB/GBL, ketamine, and other substances; polydrug combinations substantially increase overdose risk through cardiovascular and CNS depression masking.supported
Narrative review of clinical pharmacology of chemsex drugs including synthetic cathinones (3-MMC), GHB/GBL, ketamine, methamphetamine, MDMA, cocaine. Covers polydrug interactions, serotonin syndrome risk, and psychopathological outcomes. brainsci15050424
Alcohol was present in the first published fatal 3-MMC case alongside 5-APB, but the independent contribution of alcohol to the fatal outcome cannot be determined from a single polydrug case.supported
Patient administered ~500mg 3-MMC + 400mg 5-APB + 80g ethyl alcohol. j.forsciint.2014.10.016
The involvement of CYP2D6 in 3-MMC metabolism raises theoretical interaction potential with potent CYP2D6 inhibitors (SSRIs including fluoxetine and paroxetine, bupropion, quinidine)supported
CYP2D6 and CYP2E1 are implicated in metabolism. s00204-019-02539-x
The dose-dependent cardiovascular stimulation documented in the controlled trial — even at the modest doses of 25–100 mg — confirms direct cardiovascular stress that could precipitate acute coronary events, hypertensive crisis, or arrhythmia in predisposed individuals.supported
assessed the impact of three escalating doses of 3-MMC (25, 50 and 100 mg) on vital signs, neurocognitive function... s41386-024-02042-7
Hepatic impairment: The documented hepatotoxicity via CYP2D6/CYP2E1-mediated metabolic activation suggests that individuals with compromised hepatic function face elevated risk of liver injurysupported
3-MMC induces hepatotoxicity via oxidative stress, apoptosis, and autophagy in rat hepatocytes. CYP2D6 and CYP2E1 are implicated in metabolism. s00204-019-02539-x
pharmacology17 · 10 ok
Systematic structure-activity studies established the following transporter releasing potencies:supported
SAR study of 15 methcathinone analogs at DAT, NET, SERT. 3-MMC (compound 3c): DAT EC50=28±6 nM, NET EC50=27±4 nM, SERT EC50=268±25 nM. acschemneuro.8b00524
The resulting DAT:SERT selectivity ratio of approximately 9.6 places 3-MMC firmly in the catecholamine-preferring rangesupported
9.6-fold DAT:SERT selectivity. Acts primarily as releasing agent. acschemneuro.8b00524
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Blood concentrations from case reports provide limited pharmacokinetic reference points but no systematic dose-concentration relationship: 800 ng/mL in a fatal single-drug case, 1.6 µg/mL in a fatal polydrug case, 177 ng/mL in a non-fatal chemsex intoxication, and urine concentrations of 670 µg/mL in a methadone maintenance patientsupported
Fatal case of suicide poisoning with 3-MMC. Blood concentration 800 ng/ml, vitreous humor 153 ng/ml, gastric contents 5.5 mg. j.forsciint.2019.02.040
Blood concentrations from case reports provide limited pharmacokinetic reference points but no systematic dose-concentration relationship: 800 ng/mL in a fatal single-drug case, 1.6 µg/mL in a fatal polydrug case, 177 ng/mL in a non-fatal chemsex intoxication, and urine concentrations of 670 µg/mL in a methadone maintenance patientsupported
Post-mortem blood: 3-MMC 1.6 µg/mL, 5-APB 5.6 µg/mL. First report of blood concentrations in fatal 3-MMC intoxication. j.forsciint.2014.10.016
Blood concentrations from case reports provide limited pharmacokinetic reference points but no systematic dose-concentration relationship: 800 ng/mL in a fatal single-drug case, 1.6 µg/mL in a fatal polydrug case, 177 ng/mL in a non-fatal chemsex intoxication, and urine concentrations of 670 µg/mL in a methadone maintenance patientsupported
31-year-old male intoxicated with 3-MMC (177 ng/mL blood) and GHB (131 mg/L) during slamsex session. j.forsciint.2021.110743
Blood concentrations from case reports provide limited pharmacokinetic reference points but no systematic dose-concentration relationship: 800 ng/mL in a fatal single-drug case, 1.6 µg/mL in a fatal polydrug case, 177 ng/mL in a non-fatal chemsex intoxication, and urine concentrations of 670 µg/mL in a methadone maintenance patientsupported
3-MMC detected in urine of methadone maintenance patient at 670 µg/mL, along with pentedrone and methcathinone. bcpt.13270
Claim in pharmacology — inconclusiveinconclusiveworking →
Three primary Phase I metabolites have been confirmed in human biological samples (plasma, urine, saliva, hair; n=31):supported
Three biotransformation products identified: hydroxylated (C11H15NO2), keto-reduced (C11H17NO), and N-desmethyl (C10H13NO) derivatives. Confirmed in vivo in human plasma, urine, saliva and hair (n=31). j.jpba.2024.116335
Claim in pharmacology — inconclusiveinconclusiveworking →
A broader in vitro metabolic profiling study using human liver microsomes identified 25 Phase I metabolites of 3-MMC, with no sex-specific differences observed.supported
25 metabolites identified. 7 sex-specific metabolites in male rat microsomes only; no sex-specific differences in human liver microsomes. s00216-023-04815-3
CYP2D6 and CYP2E1 have been implicated in 3-MMC metabolism through hepatotoxicity studies: inhibition of either enzyme significantly reduced 3-MMC-mediated cell death in rat hepatocytes, indicating both contribute to metabolic activation generating hepatotoxic species. The precise metabolic contribution of each CYP isoform to overall drug clearance in humans has not been determined — CYP involvement is inferred from toxicity modulation, not from direct pharmacokinetic studies.supported
CYP2D6 and CYP2E1 are implicated in metabolism. Toxicity perceived at lysosome at lower concentrations, mitochondria at higher concentrations. s00204-019-02539-x
Related cathinone analogues (3-CMC, 4-CMC) share similar major metabolic pathways — keto reduction and N-demethylation — consistent with a class-level metabolic pattern for methcathinone derivatives.supported
Metabolite profiling for methcathinone analogues (3-CMC, 4-CMC, 4-BMC). Major reactions: ketoreduction and N-demethylation. s12248-024-00940-8
summary11 · 11 ok
A triple monoamine releasing agent with approximately 10-fold selectivity for catecholamine transporters over serotonin (DAT EC50 28 nM, NET EC50 27 nM, SERT EC50 268 nM), 3-MMC produces a short-duration experience of 4–6 hours by the oral route, positioning it among the shorter-acting compounds in the synthetic cathinone class.partially supported
3-MMC (compound 3c): DAT EC50=28±6 nM, NET EC50=27±4 nM, SERT EC50=268±25 nM. 9.6-fold DAT:SERT selectivity. Acts primarily as releasing agent. acschemneuro.8b00524
By 2021 it had become the most prevalent new psychoactive substance detected in European wastewater surveillancesupported
Wastewater-based epidemiology in 12 European cities (2021). 3-MMC was the most common NPS found with highest mass loads (up to 24.8 mg/day/1000 inhabitants). j.watres.2024.121390
The first controlled human pharmacology studies were published in 2025, and 3-MMC is now internationally scheduled under the Convention on Psychotropic Substances (Schedule II, 2023).partially supported
To date, there are no clinical studies that have evaluated the risk profile of 3-MMC in the recreational range of low to moderate doses. The current, first-in-human study (N=14)... s41386-024-02042-7
3-MMC acts primarily through substrate-type releasing activity at the dopamine, norepinephrine, and serotonin transporters, with a DAT:SERT selectivity ratio of approximately 9.6supported
9.6-fold DAT:SERT selectivity. Acts primarily as releasing agent. acschemneuro.8b00524
This catecholamine-dominant profile places it in the amphetamine-like cathinone subgroup rather than the MDMA-like or cocaine-like subgroupssupported
Cathinone and methcathinone acted as preferential DA/NA uptake inhibitors. Classifies cathinones into three pharmacological groups. j.1476-5381.2012.02145.x
Unlike classical amphetamines, 3-MMC is essentially inactive at trace amine-associated receptor 1 (TAAR1; EC50 >10,000 nM at human TAAR1).supported
Cathinone derivatives including mephedrone exhibited weak (EC50=5-10 µM) to negligible (EC50>10 µM) TAAR1 activity. Amphetamines showed much stronger TAAR1 activation. jpet.115.229765
At oral doses of 25–100 mg, the controlled clinical profile is characterized by dose-dependent psychostimulation — enhanced processing speed, cognitive flexibility, and psychomotor function — alongside moderate mood elevation, mild dissociative and psychotomimetic effects, and significant analgesiapartially supported
assessed the impact of three escalating doses of 3-MMC (25, 50 and 100 mg) on vital signs, neurocognitive function, state of consciousness, appetite and drug desire, in a cross-over, placebo-controlled trial. s41386-024-02042-7
At oral doses of 25–100 mg, the controlled clinical profile is characterized by dose-dependent psychostimulation — enhanced processing speed, cognitive flexibility, and psychomotor function — alongside moderate mood elevation, mild dissociative and psychotomimetic effects, and significant analgesiapartially supported
The present study assessed the analgesic effects of low to moderate doses (25, 50 and 100 mg) of 3-MMC in healthy volunteers (N=14) in a cross-over, placebo-controlled study. s00213-025-06798-8
Hepatotoxicity occurs through CYP2D6- and CYP2E1-mediated metabolic activation, producing oxidative stress, mitochondrial damage, and apoptosis at human-relevant concentrations in rat hepatocytessupported
3-MMC induces hepatotoxicity via oxidative stress, apoptosis, and autophagy in rat hepatocytes. CYP2D6 and CYP2E1 are implicated in metabolism. Toxicity perceived at lysosome at lower concentrations, mitochondria at higher concentrations. s00204-019-02539-x
Dependence liability is high: conditioned place preference in rats at 10 mg/kg matches methamphetamine, and compulsive redosing is widely documented in clinical case reportspartially supported
3-MMC induced CPP at 3 or 10 mg/kg in rats. fnmol.2022.975820
Dependence liability is high: conditioned place preference in rats at 10 mg/kg matches methamphetamine, and compulsive redosing is widely documented in clinical case reportspartially supported
higher craving/redosing/dependence potential than 4-MMC. Increasing treatment-seeking for problematic 3-MMC use. j.drugpo.2025.104971
neuroscience9 · 8 ok
Claim in neuroscience — inconclusiveinconclusiveworking →
The analgesic effects demonstrated at 50–100 mg oral may involve both noradrenergic descending pain modulation (via α₂ receptor activation in the spinal cord) and serotonergic contributions to the endogenous pain control system, though the precise neural mechanism has not been investigated.supported
The present study assessed the analgesic effects of low to moderate doses (25, 50 and 100 mg) of 3-MMC in healthy volunteers (N=14). s00213-025-06798-8
What is the cellular mechanism of 3-MMC analgesia? The analgesic efficacy at 50–100 mg is established, but the relative contributions of noradrenergic versus serotonergic versus dopaminergic pathways, and the relevant spinal versus supraspinal circuits, have not been delineated.supported
The present study assessed the analgesic effects of low to moderate doses (25, 50 and 100 mg) of 3-MMC in healthy volunteers (N=14) in a cross-over, placebo-controlled study. s00213-025-06798-8
3-MMC's potent DAT releasing activity (EC50 28 nM) directly potentiates dopaminergic transmission in the mesolimbic reward pathwaysupported
DAT EC50=28±6 nM... Acts primarily as releasing agent. acschemneuro.8b00524
Chronic 3-MMC administration in rats selectively reduces inhibitory synaptic transmission in the NAc, manifest as decreased spontaneous inhibitory postsynaptic current (sIPSC) amplitude without changes in excitatory transmissionsupported
Decreased sIPSC amplitude in NAc after chronic exposure. fnmol.2022.975820
The potent NET releasing activity (EC50 27 nM) drives the sympathomimetic effects observed clinically — tachycardia, hypertension, enhanced arousal, and the cognitive performance improvements documented in the controlled trialsupported
assessed the impact of three escalating doses of 3-MMC (25, 50 and 100 mg) on vital signs, neurocognitive function, state of consciousness. s41386-024-02042-7
The controlled clinical data show dose-dependent increases in both drug "liking" and "wanting", consistent with incentive salience theorysupported
assessed the impact of three escalating doses of 3-MMC (25, 50 and 100 mg) on... appetite and drug desire. s41386-024-02042-7
The documented compulsive redosing behavior supports this theoretical prediction.supported
higher craving/redosing/dependence potential than 4-MMC. Increasing treatment-seeking for problematic 3-MMC use. j.drugpo.2025.104971
The biphasic anxiety pattern observed in rats — anxiolytic effects acutely, anxiogenic effects after 7 days of dosing — is consistent with the emergence of counteradaptive processes that oppose the acute drug effectsupported
Acute 3 mg/kg produced anxiolytic effects; chronic 7-day dosing produced anxiety-like behavior. fnmol.2022.975820
history6 · 4 ok
Italy was among the earliest significant markets for 3-MMC: forensic laboratory analysis of seized NPS in 2013–2015 found that 3-MMC constituted 22% of all NPS seizuressupported
In Italy, 35/162 (22%) of seized NPS samples (2013-2015) were 3-MMC crystals. j.forsciint.2016.01.037
Wastewater-based epidemiology across 12 European cities in 2021 confirmed 3-MMC as the most prevalent new psychoactive substance in circulation, with mass loads reaching 24.8 mg/day/1,000 inhabitants — exceeding all other monitored NPS.supported
Wastewater-based epidemiology in 12 European cities (2021). 3-MMC was the most common NPS found with highest mass loads (up to 24.8 mg/day/1000 inhabitants). j.watres.2024.121390
The first controlled human pharmacology studies of 3-MMC were published in 2025 by Ramaekers and colleagues, examining dose-dependent safety, cognitive effects, and analgesic properties at 25, 50, and 100 mg oral in healthy volunteerssupported
To date, there are no clinical studies that have evaluated the risk profile of 3-MMC... The current, first-in-human study (N=14) assessed the impact of three escalating doses of 3-MMC (25, 50 and 100 mg) on vital signs, neurocognitive function, state of consciousness... s41386-024-02042-7
The first controlled human pharmacology studies of 3-MMC were published in 2025 by Ramaekers and colleagues, examining dose-dependent safety, cognitive effects, and analgesic properties at 25, 50, and 100 mg oral in healthy volunteerssupported
The present study assessed the analgesic effects of low to moderate doses (25, 50 and 100 mg) of 3-MMC in healthy volunteers (N=14) in a cross-over, placebo-controlled study. s00213-025-06798-8
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
pharmacokinetic-detail6 · 4 ok
Indirect timing data from the first-in-human clinical trial (N=14, oral doses of 25, 50, and 100 mg in a placebo-controlled crossover design) indicate:supported
first-in-human study (N=14) assessed the impact of three escalating doses of 3-MMC (25, 50 and 100 mg) on vital signs, neurocognitive function, state of consciousness, appetite and drug desire, in a cross-over, placebo-controlled trial. s41386-024-02042-7
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
In vivo metabolic profiling (n=31 samples across four biomatrices) confirms three primary Phase I pathways: keto reduction (detected in 52% of samples), N-demethylation (42%), and hydroxylation (16%). In vitro human liver microsomal studies expand the metabolic map to 25 Phase I metabolites, with no sex-specific differences in metabolite formation.partially supported
Three biotransformation products identified... Confirmed in vivo in human plasma, urine, saliva and hair (n=31). j.jpba.2024.116335
In vivo metabolic profiling (n=31 samples across four biomatrices) confirms three primary Phase I pathways: keto reduction (detected in 52% of samples), N-demethylation (42%), and hydroxylation (16%). In vitro human liver microsomal studies expand the metabolic map to 25 Phase I metabolites, with no sex-specific differences in metabolite formation.partially supported
25 metabolites identified. 7 sex-specific metabolites in male rat microsomes only; no sex-specific differences in human liver microsomes. s00216-023-04815-3
CYP2D6 and CYP2E1 are implicated in the generation of hepatotoxic metabolites based on enzyme inhibition studies in rat hepatocytessupported
CYP2D6 and CYP2E1 are implicated in metabolism. s00204-019-02539-x
receptor-pharmacology6 · 2 ok
The complete transporter interaction profile encompasses both releasing and reuptake inhibition mechanisms:supported
3-MMC (compound 3c): DAT EC50=28±6 nM, NET EC50=27±4 nM, SERT EC50=268±25 nM. Acts primarily as releasing agent. acschemneuro.8b00524
The DAT:SERT releasing EC50 ratio of ~9.6 confirms preferential catecholamine engagementsupported
9.6-fold DAT:SERT selectivity. acschemneuro.8b00524
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
comparative-pharmacology5 · 4 ok
A systematic review concluded that 3-MMC produces "more craving, more frequent re-dosing, and more dependence than 4-MMC," with treatment-seeking for 3-MMC dependence increasing in the Netherlands.supported
higher craving/redosing/dependence potential than 4-MMC. Increasing treatment-seeking for problematic 3-MMC use. j.drugpo.2025.104971
Conditioned place preference studies in rats provide a direct comparison: 3-MMC at 10 mg/kg produces CPP magnitude comparable to methamphetamine at 3 mg/kgsupported
3-MMC induced CPP at 3 or 10 mg/kg in rats. fnmol.2022.975820
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
A key pharmacological distinction lies at TAAR1: methamphetamine is a potent TAAR1 agonist, whereas 3-MMC is essentially inactive (EC50 >10,000 nM at human TAAR1)supported
Cathinone derivatives including mephedrone exhibited weak (EC50=5-10 µM) to negligible (EC50>10 µM) TAAR1 activity. Amphetamines showed much stronger TAAR1 activation. jpet.115.229765
MDMA's DAT:SERT ratio is approximately 0.1–0.3 (strongly serotonin-preferring), whereas 3-MMC's ratio of ~9.6 favors catecholamines by nearly an order of magnitudesupported
9.6-fold DAT:SERT selectivity. Acts primarily as releasing agent. acschemneuro.8b00524
effects-overview3 · 0 ok
clinical-evidence2 · 2 ok
The first-in-human study employed a randomized, double-blind, placebo-controlled, 4-way crossover design in 14 healthy volunteers receiving 25, 50, and 100 mg oral doses.supported
first-in-human study (N=14) assessed the impact of three escalating doses of 3-MMC (25, 50 and 100 mg)... in a cross-over, placebo-controlled trial. s41386-024-02042-7
A companion study using the same design examined analgesic effects:supported
The present study assessed the analgesic effects of low to moderate doses (25, 50 and 100 mg) of 3-MMC in healthy volunteers (N=14) in a cross-over, placebo-controlled study. s00213-025-06798-8
chemistry1 · 1 ok
This single-atom regiochemical difference substantially alters the pharmacological profile: 3-MMC exhibits approximately 10-fold catecholamine selectivity over serotonin, whereas mephedrone is a less selective monoamine releaser.supported
SAR study of 15 methcathinone analogs... 9.6-fold DAT:SERT selectivity. Acts primarily as releasing agent. acschemneuro.8b00524