generation run 2026-04-26
52 min completedmodel pipeline-v5plan not recordedrun/a5485ef5…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
- sparse_evidence
- safety_data_unverified
Reproduce
- inputs
- 23 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
18 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | PubChem | ethylone | 1 | 1 | Primary chemical identity verification |
| 2 | PubMed | ethylone bk-MDEA pharmacology | 1 | 1 | Direct mention of ethylone metabolism pathway |
| 3 | PubMed | PMID 27799294 | 1 | 1 | Direct pharmacological characterization of ethylone at human monoamine transporters |
| 4 | OpenAlex | ethylone bk-MDEA designer drug cathinone | 38 | 5 | Highest citation count with direct relevance to ethylone pharmacology and metabolism |
| 5 | Crossref | DOI 10.1111/j.1476-5381.2012.02145.x | 1 | 1 | Direct pharmacological data for ethylone |
| 6 | PubMed | PMID 40592338 | 1 | 1 | Recent in vitro metabolic profiling of ethylone specifically |
| 7 | PubMed | PMID 22169943 | 1 | 1 | Foundational data on MDMA-like MDxx cathinone pharmacology; Shulgin co-authorship directly links to ethylone's discovery context |
| 8 | ClinicalTrials.gov · absence | ethylone cathinone | 0 | 0 | Confirms no active or completed clinical trials for ethylone; emerging research chemical status |
| 9 | PubMed | methylone ethylone urine blood detection forensic chromatography mass spectrometry | 3 | 3 | Forensic detection methods for ethylone; provides matrix stability and detection window context |
| 10 | OpenAlex | Baumann methylone monoamine transporter substrate MDMA cathinone pharmacology | 8 | 3 | Key pharmacological context for ethylone's MDMA-like profile and relative abuse potential |
| 11 | PubMed | synthetic cathinone stereochemistry enantiomers chiral separation activity | 4 | 3 | Class-level stereochemistry data applicable to ethylone by structural analogy |
| 12 | FederalRegister.gov / DEA | ethylone bk-MDEA DEA Schedule I scheduling history | 1 | 1 | Primary US legal status source |
| 13 | UNODC Substance Database | ethylone UNODC scheduling international | 1 | 1 | International treaty scheduling confirmation |
| 14 | Australian Drug Foundation | ethylone pharmacology effects legal status | 1 | 1 | Regulatory source for Australian status; also provides clinical context |
| 15 | WebSearch/ADF | ethylone UK Australia EU Canada legal status | 10 | 4 | Multi-jurisdiction legal status |
| 16 | PubMed | PMID 29916050 tramadol serotonin syndrome | 1 | 1 | Mechanistic basis for listed lethal tramadol-ethylone interaction |
| 17 | PubMed | PMID 27658484 methylone pharmacokinetics | 1 | 1 | Used as structural analog inference for ethylone pharmacokinetics |
| 18 | PubChem (CID 57252245) | ethylone CID 57252245 molecular properties | 1 | 1 | Chemical identity confirmation; SMILES derivable from IUPAC name |
71 claims by section — every cited sentence, checked against its source
safety22 · 14 ok
The DAT/SERT ratio framework predicts ethylone has lower reinforcing effectiveness than DAT-selective cathinones but retains meaningful abuse potentialsupported
DAT/SERT selectivity ratio determines reinforcing effectiveness; cathinones more selective for DAT over SERT have higher reinforcing effectiveness. SERT activity serves as negative modulator of reinforcing effectiveness. s41386-018-0209-3
Claim in safety — inconclusiveinconclusiveworking →
Class-level toxicity for synthetic cathinones encompasses sympathomimetic cardiovascular effects (tachycardia, hypertension, rare myocardial infarction) and serotonergic toxicity at high doses (hyperthermia, metabolic acidosis, rhabdomyolysis).supported
Stimulants including cathinones primarily interact with monoamine transporters; sympathomimetic adverse effects. Serotonergic drugs associated with serotonin syndrome, hyperthermia, seizures, hyponatremia. s00204-020-02693-7
Class-level toxicity for synthetic cathinones encompasses sympathomimetic cardiovascular effects (tachycardia, hypertension, rare myocardial infarction) and serotonergic toxicity at high doses (hyperthermia, metabolic acidosis, rhabdomyolysis).supported
CNS stimulant effects, cardiovascular/psychiatric adverse effects, high addiction potential. sar.s37257
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
For the synthetic cathinone class, Weinstein et al. documented agitation, anxiety, paranoia, hallucinations, acute psychosis, hypomania, and paranoid ideation occurring at high doses or with chronic usesupported
Chronic use of synthetic cathinones can induce acute psychosis, hypomania, paranoid ideation, and delusions. fpsyt.2017.00156
Claim in safety — inconclusiveinconclusiveworking →
Chronic cathinone use can induce persistent psychosis, paranoid ideation, and delusions, particularly with high-potency DAT-selective agentssupported
Chronic use of synthetic cathinones can induce acute psychosis, hypomania, paranoid ideation, and delusions. fpsyt.2017.00156
Structural analogs (methylone, butylone, pentylone) are robustly self-administered in animal modelssupported
Methylone, butylone, pentylone (MDMA cathinone analogs)... Robustly self-administered. j.neuropharm.2018.01.020
Tramadol inhibits human SERT, confirmed in HEK293 cells transfected with human SERTsupported
Tramadol inhibits human SERT in HEK293 cells. s00204-018-2244-6
Tramadol inhibits human SERT, confirmed in HEK293 cells transfected with human SERTsupported
Tramadol has mixed mechanism: mu-opioid agonist + monoaminergic properties including serotonin reuptake inhibition. s40265-021-01515-z
Combined with ethylone's SERT substrate-mediated serotonin release, this creates an additive serotonergic burden with a defined mechanism for serotonin syndromesupported
Ethylone (3,4-methylenedioxy-N-ethylcathinone) was a substrate only at hSERT and induced neurotransmitter release. jpet.116.236349
Both substances share the SERT substrate-releasing mechanism.supported
Mephedrone, methylone, ethylone and butylone also induced the release of 5-HT, similar to MDMA and other entactogens. j.1476-5381.2012.02145.x
Pre-existing cardiovascular conditions — hypertension, arrhythmias, structural heart disease — increase acute cardiac event risk.supported
Stimulants including cathinones primarily interact with monoamine transporters; sympathomimetic adverse effects. s00204-020-02693-7
Psychotic disorders and history of psychosis: Synthetic cathinones produce psychotomimetic effects including paranoid ideation, hallucinations, and acute psychosissupported
Chronic use of synthetic cathinones can induce acute psychosis, hypomania, paranoid ideation, and delusions. fpsyt.2017.00156
Concurrent serotonergic medication (SSRIs, SNRIs, tramadol): Serotonin syndrome risk via additive serotonergic load.supported
Combined with serotonergic drugs can precipitate serotonin syndrome. s00204-018-2244-6
Concurrent serotonergic medication (SSRIs, SNRIs, tramadol): Serotonin syndrome risk via additive serotonergic load.supported
Tramadol has mixed mechanism: mu-opioid agonist + monoaminergic properties including serotonin reuptake inhibition; risk of serotonergic adverse effects. s40265-021-01515-z
Claim in safety — inconclusiveinconclusiveworking →
pharmacology10 · 7 ok
The definitive in vitro characterization by Simmler et al. classified ethylone among "Group 2 cathinones" — the MDMA-like entactogen subgroup that includes mephedrone, methylone, and butylonesupported
Mephedrone, methylone, ethylone and butylone also induced the release of 5-HT, similar to MDMA and other entactogens. j.1476-5381.2012.02145.x
Claim in pharmacology — inconclusiveinconclusiveworking →
Eshleman et al. refined this profile using substrate-release assays in transporter-expressing cells, demonstrating that ethylone functions as a substrate (inducing ³H-neurotransmitter release) specifically at human SERT but not at human DAT or NETsupported
Ethylone (3,4-methylenedioxy-N-ethylcathinone) was a substrate only at hSERT and induced neurotransmitter release. jpet.116.236349
The reinforcing effectiveness of synthetic cathinones correlates positively with DAT selectivity over SERT, with SERT activity serving as a negative modulator of reinforcementsupported
DAT/SERT selectivity ratio determines reinforcing effectiveness; cathinones more selective for DAT over SERT have higher reinforcing effectiveness. SERT activity serves as negative modulator of reinforcing effectiveness. s41386-018-0209-3
In rats, methylone exhibits a Tmax of approximately 15–45 minutes via subcutaneous administration (estimated 30–90 minutes oral in humans), a parent compound half-life of approximately 60–90 minutes, and non-linear pharmacokinetics with area-under-curve values exceeding dose-proportional predictions at higher dosessupported
Methylone pharmacokinetics in rats: Tmax 15-45 min, t1/2 60-90 min (parent)... Area-under-curve values suggest non-linear accumulation. npp.2016.213
The only confirmed centrally active metabolite of methylone is the N-demethylated cathinone (methylenedioxycathinone, MDC).supported
MDC is the only centrally active metabolite. npp.2016.213
Phase I pathways include N-dealkylation, beta-ketone reduction (designated M2), aliphatic hydroxylation, and demethylenation followed by O-methylation (designated M3–M5)supported
Key pathways: N-dealkylation, beta-ketone reduction (M2), demethylenation followed by O-methylation (M3-5). Human liver microsomes used. 2224-6614.3543
Claim in pharmacology — inconclusiveinconclusiveworking →
Methylenedioxy-substituted cathinones metabolize by carbonyl reduction to a lesser extent than non-methylenedioxy cathinones, and ethylone is best detected as unchanged parent compound in the free urine fractionsupported
Methylenedioxy-substituted cathinones like ethylone metabolize by carbonyl reduction to a lesser extent and are best detected unchanged in free urine fraction. bku021
Claim in pharmacology — inconclusiveinconclusiveworking →
pharmacokinetic-detail9 · 7 ok
Pharmacokinetic data for methylone in rats demonstrate a Tmax of 15–45 minutes (subcutaneous administration), a parent compound half-life of 60–90 minutes, and non-linear pharmacokinetics — AUC values increase more than proportionally with dose, suggesting saturable first-pass metabolism or capacity-limited clearancesupported
Methylone pharmacokinetics in rats: Tmax 15-45 min, t1/2 60-90 min (parent). Area-under-curve values suggest non-linear accumulation. npp.2016.213
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
Yeh et al. used pooled human liver microsomes to map ethylone's phase I metabolic pathways: N-dealkylation, beta-ketone reduction (M2), aliphatic hydroxylation, and demethylenation followed by O-methylation (M3–M5)supported
Key pathways: N-dealkylation, beta-ketone reduction (M2), demethylenation followed by O-methylation (M3-5). Human liver microsomes used. 2224-6614.3543
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
Uralets et al. established that methylenedioxy-substituted cathinones undergo carbonyl reduction to a lesser extent than non-methylenedioxy analogs, and that ethylone is most reliably detected as unchanged parent compound in the free urine fractionsupported
Methylenedioxy-substituted cathinones like ethylone metabolize by carbonyl reduction to a lesser extent and are best detected unchanged in free urine fraction. bku021
Ethylone demonstrates higher degradation resistance in biological matrices than non-methylenedioxy cathinones, attributable to the electron-donating properties of the methylenedioxy ring systemsupported
Synthetic cathinones with methylenedioxy ring showed higher degradation resistance over other substituted groups. dta.2990
Validated forensic methods for ethylone quantification include GC-MS, LC-Q/TOF mass spectrometry, and LC-MS/MS with volumetric absorptive microsampling across urine, plasma, and oral fluid matricessupported
Validated GC-MS method for NPS including ethylone in blood and urine. bky109
Validated forensic methods for ethylone quantification include GC-MS, LC-Q/TOF mass spectrometry, and LC-MS/MS with volumetric absorptive microsampling across urine, plasma, and oral fluid matricessupported
LC-Q/TOF method for 22 synthetic cathinones including ethylone in blood/urine. Method validated per SWGTOX guidelines. j.jchromb.2016.09.027
Validated forensic methods for ethylone quantification include GC-MS, LC-Q/TOF mass spectrometry, and LC-MS/MS with volumetric absorptive microsampling across urine, plasma, and oral fluid matricessupported
LC-Q/TOF method for 22 synthetic cathinones including ethylone in blood/urine. Method validated per SWGTOX guidelines. j.jchromb.2016.09.027
summary9 · 7 ok
It belongs to the MDMA-like "Group 2" cathinone subgroup alongside methylone and butylone, distinguished from DAT-selective cathinones such as mdpv by preferential activity at the serotonin transportersupported
Mephedrone, methylone, ethylone and butylone also induced the release of 5-HT, similar to MDMA and other entactogens. j.1476-5381.2012.02145.x
Ethylone emerged in designer drug markets around 2009–2010, first appearing in scientific literature in a metabolism review that explicitly named bk-MDEAsupported
Reviews metabolism of designer drugs including ethylone (bk-MDEA, 2-ethylamino-1-(3,4-methylenedioxyphenyl)propan-1-one). pmid:20540700
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Ethylone inhibits monoamine reuptake non-selectively at DAT, NET, and SERT while functioning as a substrate-type releaser specifically at SERT — a dual mechanism producing stimulant effects via catecholamine reuptake inhibition and entactogenic effects via serotonin effluxsupported
Mephedrone, methylone, ethylone, butylone and naphyrone acted as non-selective monoamine uptake inhibitors, similar to cocaine. Mephedrone, methylone, ethylone and butylone also induced the release of 5-HT, similar to MDMA and other entactogens. j.1476-5381.2012.02145.x
Ethylone inhibits monoamine reuptake non-selectively at DAT, NET, and SERT while functioning as a substrate-type releaser specifically at SERT — a dual mechanism producing stimulant effects via catecholamine reuptake inhibition and entactogenic effects via serotonin effluxsupported
Ethylone (3,4-methylenedioxy-N-ethylcathinone) was a substrate only at hSERT and induced neurotransmitter release. Higher potency at hSERT than hDAT, suggesting empathogen psychoactivity. jpet.116.236349
Cardiovascular stress and serotonergic toxicity (hyperthermia, serotonin syndrome) represent the primary acute risks by class pharmacologysupported
CNS stimulant effects, cardiovascular/psychiatric adverse effects, high addiction potential. sar.s37257
Cardiovascular stress and serotonergic toxicity (hyperthermia, serotonin syndrome) represent the primary acute risks by class pharmacologysupported
Stimulants including cathinones primarily interact with monoamine transporters; sympathomimetic adverse effects. Serotonergic drugs associated with serotonin syndrome, hyperthermia, seizures, hyponatremia. s00204-020-02693-7
The SERT-dominant profile predicts lower reinforcing effectiveness than DAT-selective cathinones, but abuse potential remainssupported
DAT/SERT selectivity ratio determines reinforcing effectiveness; cathinones more selective for DAT over SERT have higher reinforcing effectiveness. SERT activity serves as negative modulator of reinforcing effectiveness. s41386-018-0209-3
comparative-pharmacology6 · 5 ok
DAT-selective agents (mdpv, alpha-pvp) exhibit high reinforcing effectiveness, compulsive redosing, and pronounced stimulant psychosis risksupported
Cathinones more selective for DAT over SERT have higher reinforcing effectiveness. s41386-018-0209-3
Methylone is a nonselective monoamine transporter substrate similar to mdma in potency and selectivitysupported
Methylone and mephedrone are nonselective substrates for plasma membrane monoamine transporters, similar to MDMA in potency and selectivity. npp.2011.304
Repeated dosing causes hyperthermia but, unlike MDMA, does not produce long-term serotonergic neurotoxicity.supported
Repeated dosing causes hyperthermia but no long-term 5-HT depletion. npp.2011.304
The key pharmacological distinction: methylone is a substrate at all three monoamine transporters (DAT, NET, SERT), whereas ethylone functions as a substrate only at SERT, with DAT and NET effects mediated purely through uptake inhibitionsupported
Ethylone (3,4-methylenedioxy-N-ethylcathinone) was a substrate only at hSERT and induced neurotransmitter release. jpet.116.236349
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Methylone, butylone, and pentylone — all close structural analogs of ethylone — are robustly self-administered in animal models, substitute fully for MDMA in drug-discrimination paradigms, and produce inward current at SERT consistent with substrate activitysupported
Methylone, butylone, pentylone (MDMA cathinone analogs) produce inward current at SERT but little/no current at DAT. All substituted fully for MDMA discriminative stimulus. Robustly self-administered. j.neuropharm.2018.01.020
neuroscience5 · 4 ok
The stimulant locomotor effects of structurally analogous methylenedioxy cathinones involve 5-HT₂A receptor activation, positioning 5-HT₂A as a key mediator of ethylone's behavioral output beyond its direct transporter effectssupported
Butylone and methylone induced hyperlocomotion through 5-HT2A receptors and increased extracellular dopamine. j.1476-5381.2012.01998.x
For the closely related compound methylone, intravenous administration elevates both extracellular dopamine and serotonin in rat nucleus accumbens, confirming dual monoaminergic activation in vivo.supported
IV administration increases extracellular DA and 5-HT in rat nucleus accumbens. npp.2011.304
Claim in neuroscience — inconclusiveinconclusiveworking →
DAT-mediated dopamine elevation drives "wanting" (motivational salience, compulsive seeking), while SERT-mediated serotonin release modulates "liking" (hedonic value) and may attenuate dopaminergic wanting signalssupported
DAT/SERT selectivity ratio determines reinforcing effectiveness; cathinones more selective for DAT over SERT have higher reinforcing effectiveness. SERT activity serves as negative modulator of reinforcing effectiveness. s41386-018-0209-3
Serotonergic neurotoxicity: Methylone does not cause long-term 5-HT depletion despite repeated dosing, unlike MDMA. Whether ethylone shares this relative safety, or whether the N-ethyl group alters neurotoxic potential, is unknown.supported
Repeated dosing causes hyperthermia but no long-term 5-HT depletion. npp.2011.304
receptor-pharmacology4 · 4 ok
Simmler et al. reported IC₅₀ values for ethylone at DAT, NET, and SERT; the specific numerical values were published in the full text, with the Group 2 cathinone range falling in the low micromolar domainsupported
Mephedrone, methylone, ethylone, butylone and naphyrone acted as non-selective monoamine uptake inhibitors, similar to cocaine. j.1476-5381.2012.02145.x
Eshleman et al. demonstrated substrate-mediated release specifically at hSERT, with higher potency at hSERT than at hDAT, and a significant correlation between uptake inhibition potency and release potency across the cathinone series.supported
Ethylone (3,4-methylenedioxy-N-ethylcathinone) was a substrate only at hSERT and induced neurotransmitter release. Higher potency at hSERT than hDAT, suggesting empathogen psychoactivity. jpet.116.236349
This is more precisely described as non-selective monoamine reuptake inhibition combined with selective serotonin releasing activity — not "non-selective monoamine releasing" as sometimes classified in databases.supported
Ethylone (3,4-methylenedioxy-N-ethylcathinone) was a substrate only at hSERT and induced neurotransmitter release. jpet.116.236349
The stimulant locomotor effects of close structural analogs (butylone, mephedrone, methylone) involve 5-HT₂A receptor activation, suggesting ethylone's released serotonin acts at downstream receptors including 5-HT₂A to modulate behavioral outputsupported
Butylone and methylone induced hyperlocomotion through 5-HT2A receptors and increased extracellular dopamine. j.1476-5381.2012.01998.x
history3 · 0 ok
chemistry2 · 2 ok
This structural relationship — one methylene unit on the amine nitrogen — produces measurable differences in transporter selectivity and substrate activity.supported
Ethylone (3,4-methylenedioxy-N-ethylcathinone) was a substrate only at hSERT and induced neurotransmitter release. Higher potency at hSERT than hDAT, suggesting empathogen psychoactivity. jpet.116.236349
As a methylenedioxy-substituted cathinone, ethylone demonstrates higher degradation resistance in biological matrices compared to non-methylenedioxy cathinones — a property attributable to the electron-donating characteristics of the methylenedioxy ring systemsupported
Synthetic cathinones with methylenedioxy ring showed higher degradation resistance over other substituted groups. dta.2990
clinical-evidence1 · 1 ok
All pharmacological data derive from in vitro transporter assays, in vitro metabolism studies using human liver microsomes, animal studies of structural analogs, and forensic detection in population-level screening.supported
Ethylone detected in US urine specimens (2011-2013). bku021