PMA

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

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

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

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

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

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 →

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

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

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

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