generation run 2026-04-25
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22 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | PubChem | para-methoxyamphetamine | 1 | 1 | Only result; confirmed chemical identity |
| 2 | PubMed | p-methoxyamphetamine PMA monoamine oxidase A inhibitor Ki potency | 1 | 1 | Primary source for MAO-A Ki data |
| 3 | PubMed | para-methoxyamphetamine serotonin releasing agent transporter inhibitor | 1 | 1 | Key mechanistic paper already found |
| 4 | PubMed | PMA para-methoxyamphetamine MAO monoamine oxidase inhibition serotonin | 1 | 1 | Directly relevant to PMA MAO-A inhibition mechanism |
| 5 | WebSearch | PMA para-methoxyamphetamine DEA Schedule I legal status UK controlled drug | 10 | 3 | Legal status information for major jurisdictions |
| 6 | PubMed | PMA para-methoxyamphetamine pharmacology toxicity | 15 | 15 | All selected as directly relevant to PMA pharmacology, toxicity, or case reports |
| 7 | OpenAlex | para-methoxyamphetamine PMA pharmacology toxicology | 10 | 3 | Selected papers with direct PMA relevance; discarded wastewater analysis and general NPS reviews |
| 8 | ClinicalTrials.gov · absence | para-methoxyamphetamine PMA | 0 | — | No trials - as expected for Schedule I drug not in clinical development |
| 9 | PubMed | para-methoxyamphetamine deaths overdose case report | 6 | 4 | Selected case reports and forensic toxicology papers directly relevant to PMA death documentation |
| 10 | PubMed | anise oil PMA precursor synthesis | 1 | 1 | — |
| 11 | ADF Australia | — | 1 | 4 | — |
| 12 | Release UK | — | 1 | 2 | — |
| 13 | WebSearch | PMA para-methoxyamphetamine UK deaths 2012 2013 | 10 | 2 | — |
| 14 | WebSearch | PMA first synthesis 1960s 1970s history discovery | 10 | 2 | — |
| 15 | WebSearch | PMA para-methoxyamphetamine DEA Schedule I scheduling history when first scheduled United States | 10 | 2 | — |
| 16 | PubMed | Byard RW PMA paramethoxyamphetamine South Australia 1998 | 2 | 2 | — |
| 17 | OpenAlex | PMA paramethoxyamphetamine serotonin syndrome death fatal overdose management | 8 | 3 | — |
| 18 | WebSearch | PMA para-methoxyamphetamine EU Europe legal status Germany Netherlands | 10 | 2 | — |
| 19 | PubMed | PMA drug discrimination stimulus properties hallucinogen | 3 | 3 | — |
| 20 | Multiple | PubChem SMILES verification and DOI verification | 3 | 1 | — |
| 21 | PubMed | PMA moclobemide 5-HT temperature elevated ambient | 2 | 1 | — |
| 22 | Erowid | — | 1 | 4 | — |
111 claims by section — every cited sentence, checked against its source
safety34 · 28 ok
Fatal blood concentrations range from 0.57 mg/L (in polydrug cases) to 27 mg/L (extreme overdose)partially supported
Three fatal PMA cases with blood concentrations 10-27 mg/L. j.legalmed.2016.06.002
Respiratory failure and arrest.supported
Fatal symptoms: respiratory distress, hyperthermia, cardiac arrest, convulsions, multiorgan failure. j.forsciint.2011.12.014
Claim in safety — inconclusiveinconclusiveworking →
Fatal blood concentrations range from 0.57 mg/L (in polydrug cases) to 27 mg/L (extreme overdose)supported
PMA 0.57-0.59 mg/L in blood; ketamine and diazepam also detected. j.forsciint.2016.06.030
The therapeutic index is described qualitatively as narrow, and PMA is consistently characterized as significantly more toxic than MDMA at equivalent doses.supported
PMA's greater SERT inhibition may account for more severe adverse reactions. pmid:15979209
The therapeutic index is described qualitatively as narrow, and PMA is consistently characterized as significantly more toxic than MDMA at equivalent doses.supported
PMA associated with more severe hyperthermia than MDMA, cocaine, methamphetamine in humans. pmid:17530474
Claim in safety — inconclusiveinconclusiveworking →
Hyperthermia: The most common lethal mechanism. Core body temperatures exceeding 40–42°C have been documented. PMA-induced hyperthermia is more severe than that produced by MDMA, cocaine, or methamphetamine, driven by combined MAO-A inhibition, 5-HT release, and disruption of thermoregulatory behavior.supported
PMA associated with more severe hyperthermia than MDMA, cocaine, methamphetamine in humans. Thermoregulatory behavior disrupted by all four drugs. pmid:17530474
Cardiovascular collapse: Acute cardiorespiratory failure is the most frequently cited cause of death in forensic studies.supported
Cause of death: acute cardiorespiratory failure. j.legalmed.2016.06.002
Claim in safety — inconclusiveinconclusiveworking →
Cardiovascular collapse: Acute cardiorespiratory failure is the most frequently cited cause of death in forensic studies.partially supported
Multiple organ failure as cause of death. pmid:12820749
Seizures: Generalized convulsions are documented in multiple fatal and near-fatal cases.supported
16-year-old male found in coma with seizures, hyperthermia. pmid:14616331
Seizures: Generalized convulsions are documented in multiple fatal and near-fatal cases.supported
Fatal symptoms: respiratory distress, hyperthermia, cardiac arrest, convulsions, multiorgan failure. j.forsciint.2011.12.014
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Nicol et al. explicitly describe PMMA/PMA exposure as producing "multiorgan dysfunction and serotonin syndrome, followed by cardiovascular collapse".supported
PMMA exposure characterized by multiorgan dysfunction and serotonin syndrome, then cardiovascular collapse. cmajo.20140070
Hypoglycemia and hyperkalemia appear specific to PMA poisoning and may represent independent risk factors in fatal cases.supported
Hypoglycaemia and hyperkalaemia noted as possibly PMA-specific. pmid:14616331
Amphetamine-class intoxication carries a pooled rhabdomyolysis incidence of 30.5% (95% CI 22.6–38.5%) in a systematic reviewsupported
amphetamines (30.5%, 95% CI 22.6-38.5%) s41598-023-45031-4
Case reports and community sources describe dose-dependent anxiety and agitation at higher doses, with animal models confirming anxiogenic effects and unique immobility at higher dosessupported
higher doses showed anxiogenic effects similar to MDMA, plus immobility unique to PMA. j.pbb.2018.02.002
Given PMA's classification as a hallucinogen in some frameworks, such risks cannot be excluded but are uncharacterized.supported
PMA classified as hallucinogen (not entactogen or stimulant) by behavioral cluster analysis. pmid:7617822
Callaghan et al. demonstrated that repeated PMA administration (10–20 mg/kg for 4 days) produced significant reductions in cortical SERT binding (53% at 20 mg/kg) without reducing cortical 5-HT contentsupported
Repeated PMA (10-20 mg/kg for 4 days) reduced cortical SERT binding (53%) but unlike MDMA did not reduce cortical 5-HT content. pmid:16925993
PMA does not maintain self-administration in rats and lacks amphetamine-like discriminative stimulus properties (only ~30% amphetamine-lever responding), indicating low reinforcing and dependence-forming potential compared to classical stimulantssupported
PMA does not maintain self-administration in rats (not reinforcing). PMA does not substitute for amphetamine in drug discrimination (only ~30%). Supports low addiction potential. pmid:1539067
PMA failed to substitute for amphetamine in rhesus monkey discrimination paradigms.supported
PMA produced little/no amphetamine-appropriate response in monkeys (up to 3-10 mg/kg). pmid:9088779
PMA is itself a potent MAO-A inhibitorsupported
PMA is 20x more potent than (+)-amphetamine as MAO-A inhibitor. pmid:6103055
Freezer et al. demonstrated that moclobemide did not further increase PMA-induced 5-HT release at room temperature, because PMA already near-saturates MAO-Asupported
Co-administration with moclobemide did not further increase PMA's 5-HT release but did for MDMA, suggesting PMA already saturates MAO-A. pmid:15804499
At elevated ambient temperature (30°C), however, moclobemide combined with PMA produced 1450% peak striatal 5-HT increase and sustained hyperthermia.supported
At elevated temperature (30°C), moclobemide + PMA produced 1450% peak 5-HT increase. pmid:17306465
Claim in safety — inconclusiveinconclusiveworking →
Tramadol, which inhibits 5-HT and NE reuptake and has weak MAO-inhibitory properties, combined with PMA would be expected to produce catastrophic serotonin syndrome based on convergent mechanistic pathways. MDMA combined with PMA is documented in multiple fatality reports: the slow onset of PMA and faster onset of MDMA means users may unknowingly combine both substances when re-dosing.supported
Death of 22-year-old after PMMA/PMA-containing ecstasy pills. Highlights that ecstasy pills may contain unexpected substances. pmid:12935573
PMA is a weak Pgp inhibitor at concentrations far exceeding typical plasma levels — clinically unlikely to affect CNS penetration of co-administered drugs.supported
Weak Pgp inhibition at concentrations higher than in vivo levels; unlikely to significantly affect brain access of co-administered drugs. pmid:14690877
Concurrent MAO inhibitor therapy (including moclobemide, phenelzine, tranylcypromine, selegiline) is an absolute contraindication: the combination dramatically amplifies serotonin syndrome risk and can be lethal at any PMA dose.supported
PMA is MAO-A inhibitor. Co-administration with moclobemide did not further increase PMA's 5-HT release but did for MDMA. pmid:15804499
Concurrent MAO inhibitor therapy (including moclobemide, phenelzine, tranylcypromine, selegiline) is an absolute contraindication: the combination dramatically amplifies serotonin syndrome risk and can be lethal at any PMA dose.supported
At elevated temperature (30°C), moclobemide + PMA produced 1450% peak 5-HT increase. pmid:17306465
Epilepsy is contraindicated given documented seizures in PMA poisoning cases.supported
16-year-old male found in coma with seizures, hyperthermia. pmid:14616331
Epilepsy is contraindicated given documented seizures in PMA poisoning cases.supported
Fatal symptoms: respiratory distress, hyperthermia, cardiac arrest, convulsions, multiorgan failure. j.forsciint.2011.12.014
Hepatic and renal impairment are relative contraindications given multi-organ failure in severe toxicity cases and the likely role of hepatic CYP2D6 in PMA metabolism.supported
CYP2D6 genetics significantly impacts PMMA metabolism. dmd.117.077263
pharmacology17 · 15 ok
Hewton et al. found in rat substantia nigra microdialysis that PMA produced a 726 ± 287% increase in extracellular 5-HT versus 482 ± 83% for MDMAsupported
PMA and MDMA both increase extracellular 5-HT (726% and 482% respectively in substantia nigra). pmid:17714093
Green and El Hait characterized PMA as having a Ki of 0.22 µM for MAO-A in mouse brain in vitro — over 20 times more potent than (+)-amphetamine as an inhibitor of 5-HT oxidationsupported
PMA is 20x more potent than (+)-amphetamine as MAO-A inhibitor. Ki = 0.22 μM for MAO-A (mouse brain). pmid:6103055
Selectivity for MAO-A over MAO-B is pronounced: Ki for MAO-B is approximately 500 µM (benzylamine substrate, rat liver mitochondria), yielding a selectivity ratio of approximately 2,300-fold. In vivo, PMA was 10 times more active than amphetamine at protecting mouse brain MAO from phenelzine inhibitionsupported
Ki ~500 μM for MAO-B. 10x more active than amphetamine in vivo protecting against phenelzine. pmid:6103055
Selectivity for MAO-A over MAO-B is pronounced: Ki for MAO-B is approximately 500 µM (benzylamine substrate, rat liver mitochondria), yielding a selectivity ratio of approximately 2,300-fold. In vivo, PMA was 10 times more active than amphetamine at protecting mouse brain MAO from phenelzine inhibitionsupported
Ki ~500 μM for MAO-B. 10x more active than amphetamine in vivo protecting against phenelzine. pmid:6103055
Freezer et al. demonstrated via rat striatal microdialysis that PMA produces approximately 360% increase in extracellular 5-HT, compared with approximately 590% for MDMA under identical conditionssupported
PMA produced 360% increase in extracellular 5-HT (MDMA 590%). pmid:15804499
PMA-evoked 5-HT release was partially blocked by a SERT inhibitor, confirming SERT-mediated efflux as the release mechanism.supported
Evoked 5-HT release via SERT mechanism. pmid:15979209
Callaghan et al., using chronoamperometry in anesthetized rats, demonstrated that while PMA causes less total neurotransmitter release than MDMA in the striatum, PMA is a more efficacious inhibitor of 5-HT clearance in the hippocampal CA3 region — a structure where only SERT (not DAT) clears serotoninsupported
PMA causes less neurotransmitter release than MDMA in striatum but is a more efficacious SERT inhibitor in hippocampus. pmid:15979209
Adding the MAO-A inhibitor clorgyline further potentiated MDMA-induced release (to 1033%) but did not potentiate PMA, because PMA already near-saturates endogenous MAO-A at the doses tested — its own MAO-A inhibitory action is already operative.supported
Adding clorgyline potentiated MDMA but not PMA (already saturating MAO-A). pmid:17714093
Gołembiowska et al. demonstrated using rat brain microdialysis that PMA (5 and 10 mg/kg) enhances dopamine and 5-HT release in the striatum, nucleus accumbens, and frontal cortex, with increased DA and 5-HT tissue content in nucleus accumbens and frontal cortexsupported
PMA (5, 10 mg/kg) enhanced DA and 5-HT release in rat striatum, nucleus accumbens, and frontal cortex via microdialysis. PMA increased DA tissue content in nucleus accumbens and frontal cortex. PMA increased 5-HT content in nucleus accumbens and frontal cortex. s12640-015-9569-1
Simmler et al. referenced PMA as releasing norepinephrine and 5-HT similarly to PMMA, 4-MTA, and MDMA in comparative in vitro transporter studies, though PMA-specific Ki/EC50 values at DAT and NET were not publishedsupported
PMA referenced as releasing NE and 5-HT similar to PMMA, 4-MTA, and MDMA in in vitro transporter studies. j.neuropharm.2013.11.008
Liechti classifies para-substituted amphetamines including PMA as serotonergic entactogens (serotonin-preferential releasing agents), similar to MDMAsupported
Para-substituted amphetamines (including PMA) classified as serotonin-releasing entactogens. smw.2015.14043
Hegadoren et al. classify PMA as a hallucinogen based on behavioral cluster analysis in rats — a classification distinct from both entactogens and stimulantssupported
PMA classified as hallucinogen (not entactogen or stimulant) by behavioral cluster analysis. PMA's behavioral profile distinct from MDMA class. pmid:7617822
Winter found PMA established clear discriminative stimulus control in rats independent of serotonergic mediation, with partial cross-generalization to LSDsupported
PMA established clear discriminative stimulus control in rats. LSD-trained subjects showed intermediate response to PMA (partial cross-generalization). PMA's LSD-like effects are serotonergically mediated but PMA's own stimulus control is not. pmid:6546992
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
PMA is a minor metabolite of PMMA via N-demethylationsupported
PMA is a minor metabolite of PMMA. dmd.117.077263
CYP2D6 is involved in PMMA metabolism producing PMA, and by structural analogy CYP2D6 likely plays a role in PMA's own further metabolismsupported
CYP2D6 genetics significantly impacts PMMA metabolism. PMA is a minor metabolite of PMMA. dmd.117.077263
neuroscience12 · 11 ok
PMA enhances DA release in the striatum, nucleus accumbens, and frontal cortex at 5 and 10 mg/kg in ratssupported
PMA (5, 10 mg/kg) enhanced DA and 5-HT release in rat striatum, nucleus accumbens, and frontal cortex via microdialysis. s12640-015-9569-1
Repeated PMA exposure (10–20 mg/kg for 4 days) produces 53% reduction in cortical SERT binding without corresponding depletion of 5-HT tissue contentsupported
Repeated PMA (10-20 mg/kg for 4 days) reduced cortical SERT binding (53%) but unlike MDMA did not reduce cortical 5-HT content. pmid:16925993
In mouse aggression models, PMA (2–12 mg/kg i.p.) reduces offensive behavior with a complex dose-dependent profile: lower doses increase social investigation, while higher doses produce anxiogenic effects and a unique immobility not seen with MDMA.supported
PMA (2-12 mg/kg i.p.) reduced offensive behaviors in mice. Complex dose-dependent profile: lowest dose showed social investigation and approach; higher doses showed anxiogenic effects similar to MDMA, plus immobility unique to PMA. j.pbb.2018.02.002
Serotonin toxicity cascade: PMA exemplifies the convergent model of serotonin syndrome pathogenesis: simultaneous release, reuptake blockade, and catabolism inhibition produce a serotonergic "triple hit" that overwhelms homeostatic regulationsupported
PMA and MDMA both increase extracellular 5-HT (726% and 482% respectively in substantia nigra). PMA has greater potency as MAO-A inhibitor. pmid:17714093
Does CYP2D6 polymorphism (poor metabolizer phenotype) influence PMA toxicity risk, as demonstrated for PMMA?supported
CYP2D6 genetics significantly impacts PMMA metabolism. dmd.117.077263
In the striatum, PMA elevates 5-HT to approximately 360% of baseline; in the substantia nigra, to 726 ± 287%supported
PMA produced 360% increase in extracellular 5-HT (MDMA 590%). pmid:15804499
In the striatum, PMA elevates 5-HT to approximately 360% of baseline; in the substantia nigra, to 726 ± 287%supported
PMA and MDMA both increase extracellular 5-HT (726% and 482% respectively in substantia nigra). pmid:17714093
The magnitude of DA release is modest compared to classical stimulants, consistent with PMA's failure to maintain self-administrationsupported
PMA does not maintain self-administration in rats (not reinforcing). Supports low addiction potential. pmid:1539067
Claim in neuroscience — inconclusiveinconclusiveworking →
Neither PMA nor the selective 5-HT neurotoxin 5,7-DHT produced increased cleaved MAP-tau, a marker of cytoskeletal disruption associated with dopaminergic neurotoxicants.supported
PMA and MDMA produce selective 5-HT depletion without affecting C-tau (CNS toxicity marker) unlike AMPH/METH. pmid:17084036
Hegadoren et al. classified PMA as a hallucinogen based on behavioral cluster analysis — distinct from both psychomotor stimulants and entactogenssupported
PMA classified as hallucinogen (not entactogen or stimulant) by behavioral cluster analysis. PMA's behavioral profile distinct from MDMA class. pmid:7617822
Incentive salience model: PMA's failure to maintain self-administration in rats despite producing conditioned place preference in zebrafish suggests a dissociation between wanting (mesolimbic DA-driven incentive salience) and liking (hedonic value)supported
PMA does not maintain self-administration in rats (not reinforcing). pmid:1539067
summary11 · 8 ok
Para-methoxyamphetamine (PMA, 4-MA) is a substituted amphetamine with stimulant and entactogenic properties, though animal behavioral data also support hallucinogenic classificationpartially supported
PMA classified as hallucinogen (not entactogen or stimulant) by behavioral cluster analysis. PMA's behavioral profile distinct from MDMA class. pmid:7617822
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
PMA acts through three converging serotonergic mechanisms: potent reversible MAO-A inhibition (Ki = 0.22 µM, >20-fold more potent than amphetamine), SERT-mediated 5-HT release producing ~360% striatal elevation in rats, and more efficacious 5-HT reuptake inhibition than MDMA in hippocampal regions served exclusively by SERTsupported
PMA is 20x more potent than (+)-amphetamine as MAO-A inhibitor. Ki = 0.22 μM for MAO-A (mouse brain). pmid:6103055
PMA acts through three converging serotonergic mechanisms: potent reversible MAO-A inhibition (Ki = 0.22 µM, >20-fold more potent than amphetamine), SERT-mediated 5-HT release producing ~360% striatal elevation in rats, and more efficacious 5-HT reuptake inhibition than MDMA in hippocampal regions served exclusively by SERTsupported
PMA produced 360% increase in extracellular 5-HT (MDMA 590%). PMA is MAO-A inhibitor. pmid:15804499
PMA acts through three converging serotonergic mechanisms: potent reversible MAO-A inhibition (Ki = 0.22 µM, >20-fold more potent than amphetamine), SERT-mediated 5-HT release producing ~360% striatal elevation in rats, and more efficacious 5-HT reuptake inhibition than MDMA in hippocampal regions served exclusively by SERTsupported
PMA causes less neurotransmitter release than MDMA in striatum but is a more efficacious SERT inhibitor in hippocampus. Evoked 5-HT release via SERT mechanism. pmid:15979209
PMA's acute toxicity is critical: fatal blood concentrations range from 0.57 to 27 mg/L, with hyperthermia exceeding 40–42°C as the primary lethal mechanism — more severe than MDMA, cocaine, or methamphetaminepartially supported
Three fatal PMA cases with blood concentrations 10-27 mg/L. Cause of death: acute cardiorespiratory failure. j.legalmed.2016.06.002
PMA's acute toxicity is critical: fatal blood concentrations range from 0.57 to 27 mg/L, with hyperthermia exceeding 40–42°C as the primary lethal mechanism — more severe than MDMA, cocaine, or methamphetaminesupported
PMA associated with more severe hyperthermia than MDMA, cocaine, methamphetamine in humans. pmid:17530474
PMA does not maintain self-administration in rats, suggesting low dependence liabilitysupported
PMA does not maintain self-administration in rats (not reinforcing)... Supports low addiction potential. pmid:1539067
Repeated administration reduces cortical SERT binding by 53% without depleting 5-HT — a tolerance mechanism distinct from MDMA's neurotoxic patternsupported
Repeated PMA (10-20 mg/kg for 4 days) reduced cortical SERT binding (53%) but unlike MDMA did not reduce cortical 5-HT content. Different long-term neurotoxic profile from MDMA. pmid:16925993
comparative-pharmacology9 · 8 ok
When PMA is unknowingly ingested as MDMA, the delayed onset triggers re-dosing before first-dose effects manifest — a dynamic consistently identified as the primary driver of fatal overdoses.supported
PMA more potent but slower onset than MDMA leads to redosing danger. j.legalmed.2016.06.002
Repeated PMA administration (10–20 mg/kg for 4 days) reduced cortical SERT binding by 53% without reducing cortical 5-HT contentsupported
Repeated PMA (10-20 mg/kg for 4 days) reduced cortical SERT binding (53%) but unlike MDMA did not reduce cortical 5-HT content. pmid:16925993
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
MDMA produces greater absolute striatal 5-HT release (~590% vs. ~360% for PMA in rat microdialysis), but PMA achieves a higher net serotonergic burden through its concurrent MAO-A inhibition (Ki = 0.22 µM) — a mechanism absent from MDMAsupported
PMA produced 360% increase in extracellular 5-HT (MDMA 590%). PMA is MAO-A inhibitor. pmid:15804499
MDMA produces greater absolute striatal 5-HT release (~590% vs. ~360% for PMA in rat microdialysis), but PMA achieves a higher net serotonergic burden through its concurrent MAO-A inhibition (Ki = 0.22 µM) — a mechanism absent from MDMAsupported
PMA is 20x more potent than (+)-amphetamine as MAO-A inhibitor. Ki = 0.22 μM for MAO-A (mouse brain). pmid:6103055
The MAO-A inhibitor clorgyline further potentiates MDMA (to 1033%) but not PMA, confirming PMA's endogenous MAO-A saturation.supported
Adding clorgyline potentiated MDMA but not PMA (already saturating MAO-A). pmid:17714093
PMA produces more severe hyperthermia than MDMA, cocaine, or methamphetamine and disrupts thermoregulatory behaviorsupported
PMA associated with more severe hyperthermia than MDMA, cocaine, methamphetamine in humans. Thermoregulatory behavior disrupted by all four drugs. pmid:17530474
MDMA under comparable regimens reduces both SERT binding and 5-HT content, consistent with frank serotonergic axonal degenerationsupported
Unlike MDMA did not reduce cortical 5-HT content. Different long-term neurotoxic profile from MDMA. pmid:16925993
PMA does not maintain self-administration in rats and produces only ~30% amphetamine-lever responding in drug discriminationsupported
PMA does not maintain self-administration in rats (not reinforcing). PMA does not substitute for amphetamine in drug discrimination (only ~30%). pmid:1539067
clinical-evidence7 · 6 ok
Forensic case reports documenting fatal and near-fatal intoxicationssupported
PMA is a substituted synthetic amphetamine with high incidence of significant morbidity and mortality in overdose. Case of PMA overdose in South Australia. pmid:12733852
Forensic case reports documenting fatal and near-fatal intoxicationssupported
Three fatal cases in Denmark 2000. Lethal blood concentrations of PMA/PMMA. pmid:12820749
Forensic case reports documenting fatal and near-fatal intoxicationssupported
Three fatal PMA cases with blood concentrations 10-27 mg/L. Cause of death: acute cardiorespiratory failure. j.legalmed.2016.06.002
In vitro receptor and transporter studiessupported
Ki = 0.22 μM for MAO-A (mouse brain). pmid:6103055
In vitro receptor and transporter studiespartially supported
Differences in the in vivo dynamics of neurotransmitter release and serotonin uptake...revealed by chronoamperometry. pmid:15979209
In vivo animal microdialysis and behavioral pharmacologysupported
PMA and MDMA both increase extracellular 5-HT (726% and 482% respectively in substantia nigra). pmid:17714093
Claim in clinical-evidence — inconclusiveinconclusiveworking →
history7 · 5 ok
Claim in history — inconclusiveinconclusiveworking →
Caldicott et al. later documented South Australian PMA overdose cases and provided management guidelines, noting the compound was known locally under the street name "death".supported
Case of PMA overdose in South Australia; review of literature and management suggestions. pmid:12733852
Johansen et al. described three Danish fatal cases from this period.supported
Three fatal cases in Denmark 2000. pmid:12820749
From July 2010 to January 2011, Norway experienced 12 fatal para-methoxymethamphetamine (PMMA) intoxications and 22 non-fatal cases within a population of 4.8 million — a concentrated epidemic that triggered broad media attention and an EMCDDA advisorysupported
12 fatal and 22 non-fatal PMMA cases in Norway July 2010-January 2011. j.forsciint.2011.12.014
PMA was detected as a metabolite in these cases at low concentrations (0.00–0.26 mg/L).supported
PMA found as PMMA metabolite (0.00-0.26 mg/L). j.forsciint.2011.12.014
Claim in history — inconclusiveinconclusiveworking →
PMA can be synthesized via the Leuckart reaction from 4-methoxyphenylacetone, itself derived from anethole — a constituent of anise oil that is cheap and largely unwatched by precursor control regimes compared to MDMA precursorssupported
PMA synthesized from anethole (anise oil) via Leuckart synthesis. Precursor anethole is cheap and unwatched unlike MDMA precursors. pmid:12742705
receptor-pharmacology7 · 7 ok
Qualitative data confirm PMA enhances DA release in the striatum, nucleus accumbens, and frontal cortex (5 and 10 mg/kg, rat microdialysis)supported
PMA (5, 10 mg/kg) enhanced DA and 5-HT release in rat striatum, nucleus accumbens, and frontal cortex via microdialysis. s12640-015-9569-1
The Ki for MAO-A is 0.22 µM (mouse brain in vitro, 5-HT substrate), making PMA over 20-fold more potent than (+)-amphetamine at this targetsupported
PMA is 20x more potent than (+)-amphetamine as MAO-A inhibitor. Ki = 0.22 μM for MAO-A (mouse brain). pmid:6103055
MAO-B affinity is negligible: Ki ≈ 500 µM (benzylamine substrate, rat liver mitochondria), yielding a selectivity ratio of approximately 2,300-fold for MAO-A over MAO-B.supported
Ki ~500 μM for MAO-B. pmid:6103055
Callaghan et al. demonstrated using in vivo chronoamperometry that PMA is a more efficacious inhibitor of 5-HT clearance than MDMA in the hippocampal CA3 region, where SERT is the sole monoamine transportersupported
PMA causes less neurotransmitter release than MDMA in striatum but is a more efficacious SERT inhibitor in hippocampus. pmid:15979209
Freezer et al. confirmed SERT-mediated release: PMA-evoked striatal 5-HT efflux (~360% of baseline) was partially blocked by a SERT inhibitor.supported
PMA produced 360% increase in extracellular 5-HT (MDMA 590%). PMA is MAO-A inhibitor. pmid:15804499
Simmler et al. noted PMA releases NE and 5-HT with a profile similar to PMMA, 4-MTA, and MDMA, but PMA-specific transporter affinity values were not reported.supported
PMA referenced as releasing NE and 5-HT similar to PMMA, 4-MTA, and MDMA in in vitro transporter studies. j.neuropharm.2013.11.008
The receptor-level basis for PMA's hallucinogenic properties — suggested by partial LSD cross-generalization in drug discrimination and 5-HT₂A/C involvement in zebrafish reward models — remains uncharacterized at the binding affinity level.supported
LSD-trained subjects showed intermediate response to PMA (partial cross-generalization). PMA's LSD-like effects are serotonergically mediated. pmid:6546992
pharmacokinetic-detail5 · 3 ok
Jang et al. detected PMA in hair samples from a fatal case, demonstrating incorporation into keratinized tissue suitable for retrospective exposure confirmation.supported
Hair analysis showed PMA at 20.1 ng/mg. First report of PMA in hair. j.forsciint.2016.06.030
The delayed onset is the primary driver of re-dosing behavior and accidental overdose.supported
PMA more potent but slower onset than MDMA leads to redosing danger. j.legalmed.2016.06.002
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
PMA is a metabolite of PMMA via CYP2D6-mediated N-demethylationsupported
PMA is a minor metabolite of PMMA. CYP2D6 genetics significantly impacts PMMA metabolism. dmd.117.077263
chemistry2 · 2 ok
This para-methoxy substitution distinguishes PMA from its N-methylated congener para-methoxymethamphetamine (PMMA), of which PMA is also a metabolite via N-demethylationsupported
PMA is a minor metabolite of PMMA. dmd.117.077263
PMA is synthesized via the Leuckart reaction from 4-methoxyphenylacetone, a precursor derived from anethole (a natural constituent of anise oil)supported
PMA synthesized from anethole (anise oil) via Leuckart synthesis. pmid:12742705