generation run 2026-04-25
58 min completedmodel pipeline-v5plan not recordedrun/eee17916…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
none raised on this run
Reproduce
- inputs
- 25 source keys (listed under Sources)
- plan
- not recorded — template version, prompt hash and git SHA are written from 2026-09 onward
- model
- pipeline-v5
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- none — agent transcripts are persisted from 2026-09 onward
20 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | ClinicalTrials.gov · absence | para-methoxymethamphetamine PMMA | 0 | 0 | — |
| 2 | PubMed | para-methoxymethamphetamine | 15 | 5 | — |
| 3 | WebSearch | PMMA para-methoxymethamphetamine legal scheduling DEA Schedule I history | 10 | 1 | — |
| 4 | PubMed | PMMA para-methoxymethamphetamine pharmacology toxicology | 3 | 3 | — |
| 5 | PubChem | para-methoxymethamphetamine | 1 | 1 | — |
| 6 | PubMed | PMID 22257968 | 1 | 1 | — |
| 7 | OpenAlex | PMMA para-methoxymethamphetamine deaths toxicity | 10 | 3 | — |
| 8 | PubMed | PMID 25844375 | 1 | 1 | — |
| 9 | PubMed | Glennon methoxymethamphetamine preliminary behavioral investigation 1988 | 1 | 1 | — |
| 10 | OpenAlex | PMMA para-methoxymethamphetamine pharmacology monoamine transporter | 10 | 0 | — |
| 11 | HandWiki | — | 1 | 1 | — |
| 12 | WebSearch | PMMA synthesis history first reported discovery | 10 | 1 | — |
| 13 | Erowid/PiHKAL | — | 1 | 1 | — |
| 14 | OpenAlex | PMA para-methoxyamphetamine monoamine oxidase inhibitor serotonin releasing fatal | 10 | 3 | — |
| 15 | WebSearch | PMMA Argentina Time Warp deaths 2016 | 10 | 0 | — |
| 16 | EUDA | — | 1 | 1 | — |
| 17 | PubMed | PMID 10515329, 11420094, 17307247, 28065556 | 4 | 4 | — |
| 18 | WebSearch | PMMA Marquis Mecke Mandelin reagent test results color | 10 | 1 | — |
| 19 | WebSearch | PMMA UK Class A Germany Anlage I Canada Schedule I legal history | 10 | 0 | — |
| 20 | PubMed | PMID 19261515, 19428944, 12726841, 12935573 | 4 | 4 | — |
91 claims by section — every cited sentence, checked against its source
pharmacology19 · 11 ok
Claim in pharmacology — inconclusiveinconclusiveworking →
The convergence of these two properties — transporter-mediated serotonin release plus inhibition of serotonin's primary catabolic enzyme — is considered responsible for PMMA's disproportionate lethality relative to mdma.supported
Discusses how MAO inhibition by ring-substituted amphetamines (including methoxy-substituted compounds) influences pharmacology and toxicity. fphar.2019.01590
PMMA acts as a substrate-type releaser at the serotonin transporter (SERT) and norepinephrine transporter (NET), with comparatively weaker activity at the dopamine transporter (DAT)supported
PMMA compared to methedrone and MDMA: NE, DA, and 5-HT releasing profiles. PMMA releases NE and 5-HT similar to PMA, 4-MTA, and MDMA. j.neuropharm.2013.11.008
PMMA acts as a substrate-type releaser at the serotonin transporter (SERT) and norepinephrine transporter (NET), with comparatively weaker activity at the dopamine transporter (DAT)supported
Para-substituted amphetamines classified as entactogens that predominantly enhance serotonin release similar to MDMA. DA/5-HT transporter ratio predicts abuse potential vs toxicity. smw.2015.14043
Gołembiowska and colleagues demonstrated via rat microdialysis that PMMA (5 and 10 mg/kg i.p.) enhanced extracellular release of both dopamine and serotonin in the striatum, nucleus accumbens, and frontal cortex, with a pattern similar to MDMAsupported
PMMA (5 and 10 mg/kg) enhanced release of DA and 5-HT in rat striatum, nucleus accumbens, and frontal cortex, similar to MDMA. s12640-015-9569-1
PMMA inhibits MAO-A, the enzyme responsible for catabolising serotonin, norepinephrine, and dopamine in the synapsesupported
Discusses how MAO inhibition by ring-substituted amphetamines (including methoxy-substituted compounds) influences pharmacology and toxicity. fphar.2019.01590
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Páleníček and colleagues found that serum peaks occurred at approximately 30 minutes, but brain concentrations at the higher dose (20 mg/kg) peaked at approximately 60 minutes — delayed relative to the 5 mg/kg dose, suggesting dose-dependent brain penetration kineticssupported
Serum peak ~30 min; brain peak delayed to ~1h at 20 mg/kg dose. j.pbb.2010.12.011
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
The catechol metabolite di-OH-MA — hypothesised to mediate MDMA neurotoxicity — is produced from PMMA at 2–7× lower levels than from an equimolar dose of MDMA, arguing against catechol metabolites as the primary determinant of PMMA lethality.supported
Catechol metabolite di-OH-MA not major determinant of fatal toxicity. dmd.117.077263
Phase II metabolism is limited, and PMMA displays a slow metabolic rate in vitro, potentially contributing to drug accumulation.supported
Limited Phase II metabolism. Slow metabolic rate for PMMA. j.jpba.2015.06.016
In rat urine, Staack and colleagues identified pholedrine (p-hydroxy-N-methylphenethylamine) as the major metabolite from O-demethylation, along with PMA, 1-hydroxypholedrine diastereomers (including oxilofrine), and methoxy-hydroxy metabolitessupported
PMMA metabolized by O-demethylation to pholedrine (major pathway); minor: PMA, 1-hydroxypholedrine, oxilofrine, 4'-hydroxy-3'-methoxymethamphetamine. pmid:12726841
The metabolic overlap between PMMA, PMA, and pholedrine presents a forensic differentiation challenge.supported
PMMA metabolized by O-demethylation to pholedrine (major pathway); minor: PMA... GC-MS STA method detects PMMA metabolites in urine. pmid:12726841
PMMA is a substrate of organic cation transporter 2 (OCT2) with Km in the 7.9–46 µM range; OCT2 mediates renal tubular uptake and excretionsupported
PMMA is a substrate of OCT2 (Km 7.9-46 µM range). OCT2 involvement in renal excretion of PMMA and other psychostimulants. fphar.2020.609811
Claim in pharmacology — inconclusiveinconclusiveworking →
safety17 · 11 ok
The mouse LD₅₀ is 63 mg/kg (isolated) and 53 mg/kg (aggregated) — notably, PMMA did not demonstrate the enhanced aggregation toxicity characteristic of amphetamine, suggesting its lethality operates through different mechanisms than catecholaminergic overstimulation.supported
LD50 isolated 63 mg/kg, aggregated 53 mg/kg in mice. pmid:3252264
In the Norwegian epidemic, fatal peripheral blood PMMA concentrations ranged from 0.6 to 3.1 mg/L, with a median of 1.92 mg/L (range 0.17–3.30)supported
Median fatal blood concentration 1.92 mg/L (range 0.17-3.30). Lethal range 0.6-3.1 mg/L peripheral blood. j.forsciint.2011.12.014
Death from PMMA intoxication follows a characteristic clinical trajectory:supported
Symptoms: respiratory distress, hyperthermia, cardiac arrest, convulsions, multiorgan failure. j.forsciint.2011.12.014
Death from PMMA intoxication follows a characteristic clinical trajectory:supported
PMMA exposure characterized by multiorgan dysfunction and serotonin syndrome, followed by cardiovascular collapse. cmajo.20140070
Claim in safety — inconclusiveinconclusiveworking →
PMMA causes dopaminergic striatal neuron loss in mice through a PKCδ–TNF-α-mediated mitochondrial stress pathwaysupported
PMMA treatment causes PKCδ phosphorylation, mitochondrial translocation, oxidative stress (mitochondria > cytosol), reduced mitochondrial membrane potential, complex I activity. PKCδ and TNF-α knockout protect against PMMA neurotoxicity. j.neuint.2016.09.008
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Documented fatal combinations include PMMA + mdma (Norwegian and Canadian epidemics), PMMA + pma (German fatal case), and PMMA + amphetamine (Norwegian and Canadian cases)supported
Multiple synthetic amphetamines present on toxicological analysis. cmajo.20140070
Documented fatal combinations include PMMA + mdma (Norwegian and Canadian epidemics), PMMA + pma (German fatal case), and PMMA + amphetamine (Norwegian and Canadian cases)supported
22-year-old man died after ingesting ecstasy pills containing PMMA and PMA. Femoral blood PMMA 0.85 mg/L, PMA 0.61 mg/L, amphetamine 0.21 mg/L. pmid:12935573
Because PMMA is primarily metabolised by CYP2D6, co-administration of CYP2D6 inhibitors — including fluoxetine, paroxetine, bupropion, haloperidol, and ritonavir — could markedly reduce PMMA clearance and elevate blood concentrations into the lethal rangesupported
CYP2D6 genetics significantly influences PMMA metabolism. dmd.117.077263
Claim in safety — inconclusiveinconclusiveworking →
Co-ingestion of cocaine, amphetamine, or methamphetamine carries additive cardiovascular and hyperthermia risksupported
PMMA exposure characterized by multiorgan dysfunction and serotonin syndrome, followed by cardiovascular collapse. Multiple synthetic amphetamines present on toxicological analysis. cmajo.20140070
CYP2D6 poor metabolizer status: Genetically impaired PMMA clearance increases blood concentrations and toxicity risk at any dosesupported
CYP2D6 genetics significantly influences PMMA metabolism. dmd.117.077263
Renal impairment: OCT2-mediated renal excretion may be compromised, reducing drug eliminationsupported
OCT2 involvement in renal excretion of PMMA and other psychostimulants; polymorphic OCT2 may contribute to individual toxicity differences. fphar.2020.609811
summary10 · 5 ok
Claim in summary — inconclusiveinconclusiveworking →
PMMA's research significance is almost entirely forensic and toxicological: a series of mass-casualty events — 12 deaths in Norway (2010–2011), 21 in Canada (2011), and additional fatalities across Europe and South America — established PMMA as one of the most dangerous adulterants in the illicit MDMA supply.supported
12 fatal and 22 non-fatal PMMA cases in Norway (Jul 2010-Jan 2011). j.forsciint.2011.12.014
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
The mouse LD₅₀ is 53–63 mg/kg, and fatal human blood concentrations begin at 0.6 mg/L in peripheral bloodsupported
LD50 isolated 63 mg/kg, aggregated 53 mg/kg in mice. pmid:3252264
The mouse LD₅₀ is 53–63 mg/kg, and fatal human blood concentrations begin at 0.6 mg/L in peripheral bloodsupported
Lethal range 0.6-3.1 mg/L peripheral blood. j.forsciint.2011.12.014
Death results from hyperthermia, serotonin syndrome, and cardiovascular collapse, often compounded by delayed brain penetration that encourages lethal redosingsupported
Hyperthermia only at 20 mg/kg under crowded conditions. Serum peak ~30 min; brain peak delayed to ~1h at 20 mg/kg dose. j.pbb.2010.12.011
CYP2D6 poor metabolizers face elevated risk from standard dosessupported
CYP2D6 genetics significantly influences PMMA metabolism. dmd.117.077263
comparative-pharmacology9 · 6 ok
Both compounds appear in clandestine tablets, sometimes together — the German fatal case documented co-presence of PMMA 0.85 mg/L and PMA 0.61 mg/Lsupported
22-year-old man died after ingesting ecstasy pills containing PMMA and PMA. Femoral blood PMMA 0.85 mg/L, PMA 0.61 mg/L. pmid:12935573
Not amphetamine-like and not DOM-like at doses up to 30 mg/kgsupported
Racemic PMMA produced neither DOM-like nor amphetamine-like stimulus effects. PMMA did not produce significant locomotor stimulation at doses up to 30 mg/kg. pmid:3252264
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
The combination of MAO-A inhibition plus SERT-mediated release is the defining toxicological distinctionsupported
Discusses how MAO inhibition by ring-substituted amphetamines (including methoxy-substituted compounds) influences pharmacology and toxicity. fphar.2019.01590
The catechol metabolite di-OH-MA — implicated in MDMA neurotoxicity — is produced from PMMA at 2–7× lower levels, suggesting different neurotoxicity pathways.supported
Catechol metabolite di-OH-MA not major determinant of fatal toxicity. dmd.117.077263
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Similar to but non-identical with MDMA — PMMA and MDMA fail to fully cross-generalisesupported
PMMA and MDMA stimuli are similar but non-identical. PMMA stimulus failed to generalize completely to cocaine, 8-OH DPAT, or R(-)MMA. pmid:17307247
Shared with MBDB, 3,4-DMA, and both MDMA enantiomers, placing PMMA in the "MDMA-like" (entactogen) stimulus classsupported
PMMA stimulus (ED50=0.4 mg/kg) generalized to S(+)-MBDB, R(-)-MBDB, S(+)-3,4-DMA, R(-)-3,4-DMA. Evidence that PMMA, MBDB, 3,4-DMA, and MDMA share common stimulus effects distinct from DOM and amphetamine. pmid:11420094
pharmacokinetic-detail9 · 6 ok
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
The only human pharmacological data points are from Shulgin's self-experiment (total duration ~4 hours at 110 mg oral) and post-mortem blood concentrations from fatal cases.supported
12 fatal and 22 non-fatal PMMA cases in Norway (Jul 2010-Jan 2011). Median fatal blood concentration 1.92 mg/L (range 0.17-3.30). j.forsciint.2011.12.014
CYP2D6 is the primary enzyme metabolising PMMA in human liver microsomessupported
PMMA metabolized mainly to 4-hydroxymethamphetamine (OH-MA) in HLMs; PMA as minor metabolite. CYP2D6 genetics significantly influences PMMA metabolism. dmd.117.077263
CYP2D6 inhibitors (fluoxetine, paroxetine, bupropion, haloperidol, ritonavir) could phenocopy poor-metabolizer status, raising PMMA blood concentrations in otherwise normal metabolizerssupported
CYP2D6 genetics significantly influences PMMA metabolism. dmd.117.077263
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
Aromatic hydroxylation (major): PMMA → 4-hydroxymethamphetamine (OH-MA)supported
PMMA metabolized mainly to 4-hydroxymethamphetamine (OH-MA) in HLMs. dmd.117.077263
N-dealkylation (minor): PMMA → PMAsupported
PMA as minor metabolite. dmd.117.077263
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
Phase II metabolism: limitedsupported
Limited Phase II metabolism. Slow metabolic rate for PMMA. j.jpba.2015.06.016
neuroscience8 · 6 ok
Gołembiowska and colleagues demonstrated via microdialysis in freely moving rats that PMMA (5 and 10 mg/kg i.p.) produced region-specific monoamine release patternssupported
PMMA (5 and 10 mg/kg) enhanced release of DA and 5-HT in rat striatum, nucleus accumbens, and frontal cortex, similar to MDMA. s12640-015-9569-1
Claim in neuroscience — inconclusiveinconclusiveworking →
Páleníček and colleagues further demonstrated that PMMA (20 mg/kg) produced hyperthermic responses only under crowded conditions and not in isolated housingsupported
Hyperthermia only at 20 mg/kg under crowded conditions. j.pbb.2010.12.011
Does CYP2D6 polymorphism explain inter-individual variation in fatality? Fatal cases occur across a wide blood concentration range (0.17–3.30 mg/L); pharmacogenomic profiling of fatal versus non-fatal cases has not been systematically performed.supported
Median fatal blood concentration 1.92 mg/L (range 0.17-3.30). j.forsciint.2011.12.014
Shin and colleagues established a detailed molecular mechanism for PMMA-induced neurotoxicity in micesupported
PMMA treatment causes PKCδ phosphorylation, mitochondrial translocation, oxidative stress (mitochondria > cytosol), reduced mitochondrial membrane potential, complex I activity. PKCδ and TNF-α knockout protect against PMMA neurotoxicity. j.neuint.2016.09.008
Dopaminergic striatal neuron losssupported
PKCδ and TNF-α knockout protect against PMMA neurotoxicity. j.neuint.2016.09.008
Critically, both PKCδ knockout and TNF-α knockout mice were protected from PMMA-induced apoptosis and dopaminergic neuronal loss, establishing the PKCδ–TNF-α axis as a necessary mediator of PMMA neurotoxicitysupported
PKCδ and TNF-α knockout protect against PMMA neurotoxicity. j.neuint.2016.09.008
Claim in neuroscience — inconclusiveinconclusiveworking →
history6 · 4 ok
The earliest peer-reviewed investigation of PMMA was conducted by Glennon and colleagues in 1988, who characterised its stimulus properties, locomotor effects, and acute toxicity in micesupported
Racemic PMMA produced neither DOM-like nor amphetamine-like stimulus effects. LD50 isolated 63 mg/kg, aggregated 53 mg/kg in mice. PMMA did not produce significant locomotor stimulation at doses up to 30 mg/kg. pmid:3252264
The clinical presentation was characterised by multiorgan dysfunction, serotonin syndrome, and cardiovascular collapse.supported
PMMA exposure characterized by multiorgan dysfunction and serotonin syndrome, followed by cardiovascular collapse. cmajo.20140070
A German case in 2003 documented the death of a 22-year-old male with femoral blood concentrations of PMMA 0.85 mg/L and PMA 0.61 mg/L after ingestion of a single ecstasy tabletsupported
22-year-old man died after ingesting ecstasy pills containing PMMA and PMA. Femoral blood PMMA 0.85 mg/L, PMA 0.61 mg/L, amphetamine 0.21 mg/L, ethanol 0.46 per thousand. pmid:12935573
Synthesis routes documented in forensic chemistry literature show that PMMA can be produced via the Leuckart reaction from 4-methoxyphenyl-2-propanone (PMP2P), which is obtainable from trans-anethole (extracted from star anise) or from 4-methoxytoluene — both unrestricted chemicals in many jurisdictions as of 2017supported
PMMA synthesized from star anise (trans-anethole) and 4-methoxytoluene via Leuckart reaction. Both starting materials unrestricted in many jurisdictions. j.forsciint.2016.11.041
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
receptor-pharmacology6 · 4 ok
PMMA functions as a substrate-type releaser at SERT and NET, with weaker activity at DATsupported
PMMA releases NE and 5-HT similar to PMA, 4-MTA, and MDMA. j.neuropharm.2013.11.008
PMMA functions as a substrate-type releaser at SERT and NET, with weaker activity at DATsupported
Para-substituted amphetamines classified as entactogens that predominantly enhance serotonin release similar to MDMA. DA/5-HT transporter ratio predicts abuse potential vs toxicity. smw.2015.14043
Available evidence indicates that receptor binding affinities at serotonergic and adrenergic sites are low, with transporter-mediated mechanisms predominating over direct receptor agonism.supported
PMMA compared to methedrone and MDMA: NE, DA, and 5-HT releasing profiles. PMMA releases NE and 5-HT similar to PMA, 4-MTA, and MDMA. j.neuropharm.2013.11.008
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
PMMA's selectivity profile — SERT/NET-preferring release with minimal DAT activity — places it in the entactogen pharmacological class alongside MDMA, MBDB, and related compoundssupported
PMMA discussed as MDMA analogue with entactogenic properties. Review of structure-activity relationships for entactogens. 1570159x11311050007
clinical-evidence5 · 3 ok
Vevelstad and colleagues documented 12 deaths and 22 non-fatal intoxications over six monthssupported
12 fatal and 22 non-fatal PMMA cases in Norway (Jul 2010-Jan 2011). j.forsciint.2011.12.014
Claim in clinical-evidence — inconclusiveinconclusiveworking →
Femoral blood concentrations were PMMA 0.85 mg/L and PMA 0.61 mg/Lsupported
Femoral blood PMMA 0.85 mg/L, PMA 0.61 mg/L, amphetamine 0.21 mg/L, ethanol 0.46 per thousand. pmid:12935573
Claim in clinical-evidence — inconclusiveinconclusiveworking →
Multiple synthetic amphetamines were co-present in toxicological analysis in most cases.supported
Multiple synthetic amphetamines present on toxicological analysis. cmajo.20140070
chemistry2 · 1 ok
Drug discrimination studies in rats established that the S(+)-enantiomer is the pharmacologically active isomer (ED₅₀ = 0.32 mg/kg), essentially equipotent with the racemate (ED₅₀ = 0.41 mg/kg), while R(−)-PMMA failed to produce complete stimulus generalisationsupported
S(+)PMMA (ED50 = 0.32 mg/kg) at least as potent as racemic PMMA (ED50 = 0.41 mg/kg). R(-)PMMA failed to produce complete stimulus generalization. pmid:10515329
Claim in chemistry — inconclusiveinconclusiveworking →