generation run 2026-05-03
387 min completedmodel pipeline-v5plan not recordedrun/07c47009…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
- sparse_evidence
Reproduce
- inputs
- 26 source keys (listed under Sources)
- plan
- not recorded — template version, prompt hash and git SHA are written from 2026-09 onward
- model
- pipeline-v5
- streams
- none — agent transcripts are persisted from 2026-09 onward
17 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | PubMed | PMID 2881002 | 1 | 1 | — |
| 2 | ClinicalTrials.gov · absence | MDEA methylenedioxyethylamphetamine MDE | 0 | 0 | — |
| 3 | PubChem | MDEA | 1 | 0 | — |
| 4 | PubMed | MDEA methylenedioxyethylamphetamine toxicity fatality death case report | 1 | 1 | — |
| 5 | PubMed | PMID 15179441 | 1 | 1 | — |
| 6 | WebSearch | MDEA Schedule I DEA legal status UK Misuse of Drugs Act | 10 | 2 | — |
| 7 | PubChem | 1-(1,3-benzodioxol-5-yl)-N-ethylpropan-2-amine | 1 | 1 | — |
| 8 | PubMed | methylenedioxyethylamphetamine human pharmacokinetics plasma | 9 | 5 | — |
| 9 | PubMed | methylenedioxyethylamphetamine neurotoxicity serotonin | 10 | 4 | — |
| 10 | OpenAlex | MDEA 3,4-methylenedioxyethylamphetamine pharmacology entactogen | 10 | 3 | — |
| 11 | PubMed | MDEA MDE methylenedioxyethylamphetamine pharmacology | 15 | 3 | — |
| 12 | PubMed | Gouzoulis methylenedioxyethylamphetamine human neuroendocrine | 1 | 1 | — |
| 13 | PubMed | PMID 9005345 | 1 | 1 | — |
| 14 | WebSearch | MDEA partial releaser dopamine EC50 622 nM | 10 | 1 | — |
| 15 | PubMed | PMID 2880735 | 1 | 1 | — |
| 16 | WebSearch | MDEA scheduling history US UK Germany legal status | 10 | 3 | — |
| 17 | PubMed | methylenedioxy analogues amphetamine defining risks humans | 1 | 1 | — |
102 claims by section — every cited sentence, checked against its source
safety22 · 13 ok
MDEA produces dose-dependent hyperthermia in rats: at 35 mg/kg in dark Agouti rats, peak hyperthermia was comparable in magnitude and duration to that produced by 15 mg/kg mdma, indicating MDEA requires approximately twice the dose of MDMA for equivalent hyperthermic effectsupported
MDEA caused dose-dependent hyperthermia in Dark Agouti rats. MDEA ~half the potency of MDMA for acute hyperthermia. pmid:10401727
Claim in safety — not_supportednot supportedworking →
Hyperthermia and hyperpyrexia are documented as potentially fatal complications in human MDEA users.supported
Notes complications: anxiety/depressive syndromes, fatalities with hyperpyrexia, rhabdomyolysis, DIC syndrome, hepatotoxicity. pmid:9005345
Administration of 140 mg oral MDEA to healthy volunteers produced statistically significant tachycardia and systolic hypertensionsupported
Significant long-lasting increases in serum cortisol, prolactin, systolic blood pressure, and heart rate. pmid:8507346
Fatal arrhythmias have been documented in individuals with underlying cardiac disease who used MDEA or MDMA.supported
Three deaths: MDMA/MDEA contributed to death by arrhythmias in individuals with underlying cardiac disease. pmid:2881002
Rhabdomyolysis and disseminated intravascular coagulation (DIC) are documented as fatal complications of MDxx intoxication, particularly when combined with hyperthermia.supported
Notes complications: anxiety/depressive syndromes, fatalities with hyperpyrexia, rhabdomyolysis, DIC syndrome, hepatotoxicity. pmid:9005345
Dowling, McDonough, and Bost (1987) reported five deaths associated with MDMA and MDEA usesupported
Reports five deaths associated with MDMA and MDEA use. pmid:2881002
De Letter et al. (2006) documented 34 amphetamine-related fatalities in the Ghent forensic district (1976–2004), including cases involving MDEApartially supported
In 34 fatalities, amphetamines were involved (including MDA). pmid:16454462
Schifano et al. (2010) analyzed 605 ecstasy-related deaths (MDxx class including MDEA) in the United Kingdom from 1997 to 2007partially supported
605 ecstasy (MDMA and MDA)-related deaths in UK 1997-2007. 000279302
Hepatotoxicity is listed among adverse effects of the MDxx class, but no MDEA-specific hepatotoxicity case reports were identifiedsupported
Notes adverse health effects: serotonin neurotoxicity, severe psychiatric disorders, renal failure, malignant hyperthermia, hepatitis, rhabdomyolysis, DIC. pmid:15916245
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Its combination with MDEA carries lethal risk via serotonin syndrome and seizure threshold lowering.supported
Tramadol lowers seizure threshold; risk enhanced with serotonergic drugs. First reported tramadol death by serotonin-related seizure. pmid:11111800
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
MDEA is primarily metabolized by cyp3a4 and cyp2d6supported
CYP3A4 and CYP2D6 show highest contribution to both metabolic steps. dmd.108.026203
Pre-existing cardiac disease — including arrhythmia history, structural heart disease, and long QT syndrome — constitutes an absolute contraindication based on documented fatality risk in individuals with underlying cardiac pathology.supported
Three deaths: MDMA/MDEA contributed to death by arrhythmias in individuals with underlying cardiac disease. Deaths rare but possible, more common with underlying cardiac disease. pmid:2881002
Concurrent tramadol use carries lethal interaction risk through combined serotonergic mechanisms and seizure threshold lowering.supported
Tramadol lowers seizure threshold; risk enhanced with serotonergic drugs. First reported tramadol death by serotonin-related seizure. pmid:11111800
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
pharmacology18 · 12 ok
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
The potency order for dopamine release from rat striatal synaptosomes is mda > MDMA > MDEA, consistent with the finding that N-ethyl extension of the amphetamine side chain reduces dopaminergic releasing activity in brain slice preparations.supported
The potency order for inducing [3H]DA release from striatal synaptosomes was MDA > MDMA > MDEA = MDBA. pmid:11371001
The potency order for dopamine release from rat striatal synaptosomes is mda > MDMA > MDEA, consistent with the finding that N-ethyl extension of the amphetamine side chain reduces dopaminergic releasing activity in brain slice preparations.supported
N-methylation of MDA decreased DA release; alpha-ethyl extension (BDB vs MBDB) completely abolished DA release. S-(+) isomers stereostereoselective for DA release. pmid:2880735
At SERT, MDEA, MDMA, and MDA are approximately equipotent for inducing [³H]serotonin release from rat frontal cortex and hippocampal synaptosomes, with all three producing serotonin release in the micromolar concentration range in brain slice assays.supported
MDA, MDMA and MDEA were equipotent at inducing [3H]5-HT release from frontal cortex/hippocampal synaptosomes. pmid:11371001
Claim in pharmacology — inconclusiveinconclusiveworking →
MDEA is the least potent of the chemical/mdxx series at NET. [³H]Noradrenaline uptake inhibition in rat left ventricle yields an IC₅₀ of approximately 2.75 µM (-log IC₅₀ = 5.56 ± 0.08), significantly less potent than MDMA (-log IC₅₀ = 6.05), cathinone (6.03), and cocaine (6.16). [³H]Nisoxetine displacement in rat cortex gives an EC₅₀ of approximately 10.2 µM (-log EC₅₀ = 4.99 ± 0.15).supported
Potency (-log IC50) at inhibiting [3H]NA uptake in rat left ventricle: cocaine 6.16, cathinone 6.03, MDMA 6.05, MDA 5.68, MDEA 5.56. At [3H]nisoxetine displacement in cortex: cathinone 5.40, cocaine 5.04, MDEA 4.99, MDA 4.66, MDMA 4.22. pmid:12969746
MDEA is the least potent of the chemical/mdxx series at NET. [³H]Noradrenaline uptake inhibition in rat left ventricle yields an IC₅₀ of approximately 2.75 µM (-log IC₅₀ = 5.56 ± 0.08), significantly less potent than MDMA (-log IC₅₀ = 6.05), cathinone (6.03), and cocaine (6.16). [³H]Nisoxetine displacement in rat cortex gives an EC₅₀ of approximately 10.2 µM (-log EC₅₀ = 4.99 ± 0.15).supported
Potency (-log IC50) at inhibiting [3H]NA uptake in rat left ventricle: cocaine 6.16, cathinone 6.03, MDMA 6.05, MDA 5.68, MDEA 5.56. At [3H]nisoxetine displacement in cortex: MDEA 4.99. pmid:12969746
MDMA interacts with human organic cation transporters OCT1/2 and plasma membrane monoamine transporter (hPMAT) as additional low-affinity targets; MDEA may share these interactions by structural analogy, but this remains untested.supported
MDMA is potent inhibitor of hOCT1/2 and hPMAT. Interactions with low-affinity/high-capacity transporters may supplement primary monoamine transporter effects. ijms222312995
MDEA undergoes two primary Phase I metabolic pathways:supported
MDEA is mainly metabolized by N-deethylation and demethylenation. dmd.108.026203
cyp3a4 and cyp2d6 contribute most substantially to both pathways, with CYP2C19 showing pronounced enantioselective preference for S-MDEAsupported
CYP3A4 and CYP2D6 show highest contribution to both metabolic steps. S-enantiomers preferentially metabolized, especially by CYP2C19. dmd.108.026203
Both reactions preferentially process the S-enantiomer, accounting for the faster plasma clearance of S-MDE (t₁/₂ = 4.0 h) relative to R-MDE (t₁/₂ = 7.9 h) following oral administration of the racemic-mixture.supported
Plasma half-time (R)-MDE 7.9 h vs (S)-MDE 4.0 h. S-metabolite concentrations higher. pmid:12906896
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Catechol metabolites of MDEA are enantioselectively O-methylated by both soluble and membrane-bound comt, with S-enantiomers preferentially processedsupported
S-enantiomers of MDMA, MDEA, MBDB catechol metabolites preferably O-methylated by COMT. 10-fold higher affinity for membrane-bound COMT vs soluble. tx900134e
Membrane-bound COMT has approximately 10-fold higher affinity while soluble COMT has approximately 10-fold higher catalytic turnoverpartially supported
10-fold higher affinity for membrane-bound COMT vs soluble. tx900134e
These catecholic metabolites act as uncompetitive inhibitors of sCOMT-catalyzed dopamine methylation, which may have downstream implications for dopaminergic tone.supported
Catecholic metabolites are uncompetitive inhibitors of sCOMT. tx900134e
summary15 · 12 ok
The compound circulated briefly as a legal MDMA substitute following MDMA's emergency Schedule I placement in May 1985, until MDEA was itself scheduled in October 1987supported
MDEA appeared as MDMA's legal replacement after 1985 Schedule I classification. pmid:2881002
The published evidence base is sparse: one controlled human challenge study (n=8, neuroendocrine and cardiovascular endpoints only), several human pharmacokinetic studies, and rat neurotoxicity data constitute the primary literaturesupported
Double-blind placebo-controlled cross-over study: 140 mg MDE orally to 8 healthy male volunteers. Significant long-lasting increases in serum cortisol, prolactin, systolic blood pressure, and heart rate. pmid:8507346
The published evidence base is sparse: one controlled human challenge study (n=8, neuroendocrine and cardiovascular endpoints only), several human pharmacokinetic studies, and rat neurotoxicity data constitute the primary literaturesupported
Enantioselective HPLC method for MDE and metabolites HME and MDA in human plasma/urine. After 70 mg pure MDE-HCl: plasma concentration of (R)-MDE exceeded (S)-MDE. pmid:12906896
The published evidence base is sparse: one controlled human challenge study (n=8, neuroendocrine and cardiovascular endpoints only), several human pharmacokinetic studies, and rat neurotoxicity data constitute the primary literaturesupported
HPLC method validated for MDE and metabolites (HME, MDA) in human plasma. 14 volunteers in two clinical studies after 100-140 mg MDE-HCl p.o. Pharmacokinetic parameters calculated. pmid:9869367
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
It is equipotent with MDMA for serotonin release but functions as a dopamine partial releaser (DAT EC₅₀ ≈ 622 nM, E_max ≈ 61% vs MDMA EC₅₀ ≈ 108 nM, E_max ≈ 103%) and is the least potent chemical/mdxx compound at the norepinephrine transporter (IC₅₀ ≈ 2.75 µM). cyp3a4 and cyp2d6 are the primary metabolizing enzymes.partially supported
MDA, MDMA and MDEA were equipotent at inducing [3H]5-HT release from frontal cortex/hippocampal synaptosomes. The potency order for inducing [3H]DA release from striatal synaptosomes was MDA > MDMA > MDEA = MDBA. pmid:11371001
It is equipotent with MDMA for serotonin release but functions as a dopamine partial releaser (DAT EC₅₀ ≈ 622 nM, E_max ≈ 61% vs MDMA EC₅₀ ≈ 108 nM, E_max ≈ 103%) and is the least potent chemical/mdxx compound at the norepinephrine transporter (IC₅₀ ≈ 2.75 µM). cyp3a4 and cyp2d6 are the primary metabolizing enzymes.supported
Potency (-log IC50) at inhibiting [3H]NA uptake in rat left ventricle: cocaine 6.16, cathinone 6.03, MDMA 6.05, MDA 5.68, MDEA 5.56. MDEA and MDA significantly less potent than cocaine/cathinone/MDMA. pmid:12969746
It is equipotent with MDMA for serotonin release but functions as a dopamine partial releaser (DAT EC₅₀ ≈ 622 nM, E_max ≈ 61% vs MDMA EC₅₀ ≈ 108 nM, E_max ≈ 103%) and is the least potent chemical/mdxx compound at the norepinephrine transporter (IC₅₀ ≈ 2.75 µM). cyp3a4 and cyp2d6 are the primary metabolizing enzymes.supported
CYP3A4 and CYP2D6 show highest contribution to both metabolic steps. dmd.108.026203
The subjective experience occupies an intermediate position between stimulants and hallucinogens: entactogenic warmth, psychomotor stimulation, and mild perceptual alterations at common dosessupported
Both evoke psychomotor stimulation, mild alterations of perception, sensations of closeness and positive emotional state. j.1527-3458.2004.tb00007.x
The subjective experience occupies an intermediate position between stimulants and hallucinogens: entactogenic warmth, psychomotor stimulation, and mild perceptual alterations at common dosessupported
Reviews MDMA and MDE (MDEA) as entactogens between stimulants and hallucinogens. Induces pleasant emotional state, relaxation, fearlessness, happiness. pmid:9005345
Acute toxicity centers on hyperthermia, cardiovascular stress (tachycardia, systolic hypertension), and fatal arrhythmias documented in individuals with pre-existing cardiac diseasepartially supported
Three deaths: MDMA/MDEA contributed to death by arrhythmias in individuals with underlying cardiac disease. pmid:2881002
Acute toxicity centers on hyperthermia, cardiovascular stress (tachycardia, systolic hypertension), and fatal arrhythmias documented in individuals with pre-existing cardiac diseasesupported
Significant long-lasting increases in serum cortisol, prolactin, systolic blood pressure, and heart rate. pmid:8507346
Serotonergic neurotoxicity occurs in rats at approximately 25% the potency of MDMA, but no human neurotoxicity data existsupported
MDEA ~half the potency of MDMA for acute hyperthermia and ~25% the potency for 5-HT neurodegeneration. pmid:10401727
Claim in summary — inconclusiveinconclusiveworking →
comparative-pharmacology11 · 8 ok
MDEA at 35 mg/kg produced only ~20% loss of cortical and hippocampal 5-HT and 5-HIAA, compared to ~50% loss from MDMA at 15 mg/kg — placing MDEA at approximately 25% the neurotoxic potency of MDMA on a mg/kg basissupported
MDEA ~25% the potency for 5-HT neurodegeneration. MDEA 35 mg/kg caused only ~20% loss in cortex/hippocampus vs MDMA 15 mg/kg causing ~50% loss. pmid:10401727
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Series and Molliver (1994) confirmed that multiple injections of MDEA (40 mg/kg × 8) caused pronounced reduction in 5-HT immunoreactive axons in rat brain at 2 weeks post-treatment, with posterior cerebral cortex and hippocampus CA1 most affectedsupported
Multiple injections of MDE (40 mg/kg x 8) produced pronounced reduction in serotonin-immunoreactive axons in rat brain 2 weeks post-treatment, most marked in posterior cerebral cortex and hippocampus CA1. pmid:8070524
The production of mda as an active metabolite via N-deethylation parallels MDMA's production of MDA via N-demethylation, though the relative contribution of MDA to overall effects may differ given the lower MDA plasma concentrations observed (7–33 ng/ml vs parent MDE 235–465 ng/ml at 100–140 mg doses).supported
MDEA is mainly metabolized by N-deethylation and demethylenation. dmd.108.026203
The production of mda as an active metabolite via N-deethylation parallels MDMA's production of MDA via N-demethylation, though the relative contribution of MDA to overall effects may differ given the lower MDA plasma concentrations observed (7–33 ng/ml vs parent MDE 235–465 ng/ml at 100–140 mg doses).supported
Maximum plasma concentrations: MDE 235-465 ng/ml, HME 67-673 ng/ml, MDA 7-33 ng/ml. pmid:9869367
Data sources: dopamine-transporter and serotonin-transporter release; norepinephrine-transporter; brain slice release.supported
MDA, MDMA and MDEA were equipotent at inducing [3H]5-HT release from frontal cortex/hippocampal synaptosomes. The potency order for inducing [3H]DA release from striatal synaptosomes was MDA > MDMA > MDEA = MDBA. pmid:11371001
Data sources: dopamine-transporter and serotonin-transporter release; norepinephrine-transporter; brain slice release.supported
MDMA, MDA, cathinone, MDEA tested at noradrenaline transporter. Potency (-log IC50) at inhibiting [3H]NA uptake in rat left ventricle. pmid:12969746
Data sources: dopamine-transporter and serotonin-transporter release; norepinephrine-transporter; brain slice release.supported
MDA, BDB, MDMA, MBDB and enantiomers compared for [3H]5-HT and [3H]DA release from superfused rat brain slices. pmid:2880735
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
No dopaminergic terminal damage was observed.supported
No tyrosine hydroxylase differences — dopaminergic terminals spared. pmid:8070524
neuroscience10 · 5 ok
The only direct human neurobiological data come from the Gouzoulis et al. (1993) challenge study documenting prolonged increases in serum cortisol and prolactin following 140 mg oral MDEAsupported
Significant long-lasting increases in serum cortisol, prolactin, systolic blood pressure, and heart rate. pmid:8507346
No dopaminergic terminal damage has been observed at any dose testedsupported
No tyrosine hydroxylase differences — dopaminergic terminals spared. pmid:8070524
MDEA's serotonin-releasing action at serotonin-transporter, equipotent with MDMA, predicts comparable attenuation of amygdala reactivity to threatening stimulisupported
MDA, MDMA and MDEA were equipotent at inducing [3H]5-HT release from frontal cortex/hippocampal synaptosomes. pmid:11371001
Claim in neuroscience — inconclusiveinconclusiveworking →
Claim in neuroscience — inconclusiveinconclusiveworking →
Claim in neuroscience — inconclusiveinconclusiveworking →
Animal studies demonstrate that MDEA produces long-term degeneration of serotonergic axon terminals in rat cortex and hippocampus, with posterior cerebral cortex and hippocampus CA1 most severely affectedsupported
Multiple injections of MDE (40 mg/kg x 8) produced pronounced reduction in serotonin-immunoreactive axons in rat brain 2 weeks post-treatment, most marked in posterior cerebral cortex and hippocampus CA1. pmid:8070524
Claim in neuroscience — inconclusiveinconclusiveworking →
Nichols proposed that entactogens represent a distinct pharmacological class defined by preferential serotonin release combined with sufficient dopamine activity to produce a positive, emotionally engaged state without classical hallucinogenesissupported
Seminal paper coining the term 'entactogen' for a new pharmacological class including MDA and MDMA, distinguishing them from classic hallucinogens and stimulants. pmid:2880944
Claim in neuroscience — inconclusiveinconclusiveworking →
pharmacokinetic-detail10 · 8 ok
In a study of 4 subjects receiving 70 mg racemic-mixture MDE-HCl orally:partially supported
After 70 mg pure MDE-HCl: plasma concentration of (R)-MDE exceeded (S)-MDE (AUC ratio R:S = 3.1). pmid:12906896
In 14 subjects receiving 100–140 mg racemic MDE-HCl orally:supported
14 volunteers in two clinical studies after 100-140 mg MDE-HCl p.o. pmid:9869367
Stereospecific analysis at the 140 mg dose confirmed predominance of the R-enantiomer of MDE in plasma.supported
Six healthy volunteers after 140 mg racemic MDE-HCl. R-enantiomer of MDE predominant in plasma. pmid:11232860
MDEA's dependence on CYP2D6 and CYP3A4 for primary metabolism creates significant pharmacokinetic drug interaction potentialsupported
CYP3A4 and CYP2D6 show highest contribution to both metabolic steps. dmd.108.026203
The pronounced enantioselectivity in MDEA pharmacokinetics reflects differential CYP-mediated metabolism. cyp2d6 and cyp3a4 preferentially N-deethylate and O-demethylenate the S-enantiomer, resulting in faster clearance of S-MDE (t₁/₂ = 4.0 h) relative to R-MDE (t₁/₂ = 7.9 h)supported
CYP3A4 and CYP2D6 show highest contribution to both metabolic steps. S-enantiomers preferentially metabolized. Explains enantioselective pharmacokinetic properties of MDEA in vivo. dmd.108.026203
The pronounced enantioselectivity in MDEA pharmacokinetics reflects differential CYP-mediated metabolism. cyp2d6 and cyp3a4 preferentially N-deethylate and O-demethylenate the S-enantiomer, resulting in faster clearance of S-MDE (t₁/₂ = 4.0 h) relative to R-MDE (t₁/₂ = 7.9 h)supported
Plasma half-time (R)-MDE 7.9 h vs (S)-MDE 4.0 h. S-metabolite concentrations higher. pmid:12906896
CYP2C19 shows additional pronounced enantioselectivity for S-MDEA in both metabolic pathways.supported
S-enantiomers preferentially metabolized, especially by CYP2C19. dmd.108.026203
This differential processing extends to Phase II conjugation: UGT2B15 and UGT2B17 preferentially glucuronidate S-HMEA, while SULT1A3 preferentially sulfates S-DHEA. comt likewise preferentially O-methylates S-enantiomers of the catechol metabolites, with membrane-bound COMT showing approximately 10-fold higher affinity and soluble COMT approximately 10-fold higher turnover.partially supported
S-enantiomers preferably O-methylated by COMT. 10-fold higher affinity for membrane-bound COMT vs soluble. tx900134e
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
chemistry4 · 4 ok
Identification of the correct regioisomer requires chromatographic methods, as both share identical molecular weights (207 g/mol) and similar mass spectral fragmentation (m/z 72 and 135/136).supported
Mass spectral and chromatographic methods for forensic identification. MDEA has MW 207 with m/z 72 and 135/136 as major fragments. 41.5.227
The structural progression MDA → MDMA → MDEA represents successive N-alkylation of the amine nitrogen, with each step modifying monoamine transporter selectivity and subjective effect profilesupported
N-methylation of MDA decreased DA release; alpha-ethyl extension (BDB vs MBDB) completely abolished DA release. pmid:2880735
Following oral administration of racemic MDEA, the R-enantiomer predominates in plasma with an AUC ratio of R:S = 3.1 and a substantially longer half-life (R-MDE: 7.9 h vs S-MDE: 4.0 h)supported
Plasma concentration of (R)-MDE exceeded (S)-MDE (AUC ratio R:S = 3.1); plasma half-time (R)-MDE 7.9 h vs (S)-MDE 4.0 h. pmid:12906896
This enantioselective disposition reflects preferential cyp2d6- and cyp3a4-catalyzed metabolism of the S-enantiomersupported
CYP3A4 and CYP2D6 show highest contribution to both metabolic steps. S-enantiomers preferentially metabolized. dmd.108.026203
clinical-evidence4 · 4 ok
Brunnenberg and Kovar (2001): stereospecific plasma PK at 140 mg oralsupported
Chiral HPLC method for MDE and metabolites in human plasma. Six healthy volunteers after 140 mg racemic MDE-HCl. pmid:11232860
Buechler et al. (2003): enantioselective PK at 70 mg oral in 4 subjectspartially supported
After 70 mg pure MDE-HCl: plasma concentration of (R)-MDE exceeded (S)-MDE (AUC ratio R:S = 3.1). pmid:12906896
Gouzoulis et al. (1993) conducted a double-blind, placebo-controlled, crossover study administering 140 mg oral MDE-HCl or placebo to 8 healthy male volunteers.supported
Double-blind placebo-controlled cross-over study: 140 mg MDE orally to 8 healthy male volunteers. pmid:8507346
Brunnenberg et al. (1998): plasma PK of MDEA and metabolites following 100–140 mg oral in 14 subjectssupported
14 volunteers in two clinical studies after 100-140 mg MDE-HCl p.o. Maximum plasma concentrations: MDE 235-465 ng/ml, HME 67-673 ng/ml, MDA 7-33 ng/ml. pmid:9869367
history4 · 2 ok
The landmark 1987 JAMA report by Dowling, McDonough, and Bost — documenting five deaths associated with MDEA and MDMA use — drew significant public and regulatory attention to MDEA toxicity and accelerated the scheduling process.supported
Reports five deaths associated with MDMA and MDEA use. MDEA appeared as MDMA's legal replacement after 1985 Schedule I classification. pmid:2881002
Claim in history — inconclusiveinconclusiveworking →
In 1986, David Nichols coined the term "entactogen" — meaning "to produce a touching within" — to describe the pharmacological class encompassing MDEA, MDMA, and mda, distinguishing these compounds from both classical stimulants and serotonergic hallucinogens.supported
Seminal paper coining the term 'entactogen' for a new pharmacological class including MDA and MDMA, distinguishing them from classic hallucinogens and stimulants. pmid:2880944
Claim in history — inconclusiveinconclusiveworking →
receptor-pharmacology2 · 1 ok
No serotonin-transporter-specific Ki or EC₅₀ values in nM were recovered from published primary literature for MDEA. The equipotency data with MDMA and MDA derive from rat synaptosome release assays using [³H]serotonin and rat brain slice assayssupported
MDA, MDMA and MDEA were equipotent at inducing [3H]5-HT release from frontal cortex/hippocampal synaptosomes. pmid:11371001
Claim in receptor-pharmacology — not_supportednot supportedworking →
effects-overview1 · 0 ok
Claim in effects-overview — inconclusiveinconclusiveworking →
legal-status1 · 1 ok
Its scheduling followed mdma's classification and was accelerated by early reports of MDEA-associated fatalitiessupported
Reports five deaths associated with MDMA and MDEA use. MDEA appeared as MDMA's legal replacement after 1985 Schedule I classification. pmid:2881002