generation run 2026-05-03
48 min completedmodel pipeline-v5plan not recordedrun/6d47a910…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
- sparse_evidence
Reproduce
- inputs
- 22 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
22 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | PubMed | Butylone bk-MBDB pharmacology cathinone | 4 | 4 | All directly relevant to butylone pharmacology, toxicology, and safety |
| 2 | ClinicalTrials.gov · absence | butylone synthetic cathinone | 0 | — | Confirms absence of clinical trial activity |
| 3 | PubChem | Butylone | 1 | 1 | Only result; confirms seed data chemical identity |
| 4 | PubMed | PMID 33550444 | 1 | 1 | Key hepatotoxicity and CYP450 interaction data for butylone |
| 5 | PubMed | synthetic cathinone monoamine transporter binding affinity DAT SERT NET | 1 | 1 | Contains specific butylone transporter binding data |
| 6 | OpenAlex | DOI 10.1111/j.1476-5381.2012.02145.x | 1 | 1 | Landmark pharmacology paper with specific butylone data |
| 7 | OpenAlex | Butylone bk-MBDB synthetic cathinone | 10 | 5 | High-citation landmark papers directly relevant to butylone pharmacology, toxicity, and detection |
| 8 | PubMed | PMID 22160789 | 1 | 1 | Critical safety case report specifically involving butylone |
| 9 | WebSearch | butylone bk-MBDB DEA Schedule I scheduling date | 10 | 2 | Official government sources for US scheduling history |
| 10 | WebSearch/Wikipedia | butylone bk-MBDB synthesis history first synthesis year discovery | 10 | 1 | Historical synthesis and market emergence data |
| 11 | WebSearch/Erowid | butylone UK Misuse of Drugs Act scheduling | 10 | 2 | Comprehensive multi-jurisdiction legal status |
| 12 | PubMed | designer cathinone neurotoxicity oxidative stress mitochondria apoptosis | 1 | 1 | Specific neurotoxicity mechanism data for butylone |
| 13 | PubMed | synthetic cathinone reinforcing self-administration addiction abuse potential animal | 8 | 1 | Provides class-level context for cathinone abuse liability and DEA scheduling history |
| 14 | PubMed Central | PMC3550225 Warrick 2012 butylone methylone serotonin syndrome | 1 | 1 | Critical primary safety data for butylone |
| 15 | WebSearch | butylone Canada EU scheduling | 10 | — | Establishes gap in available legal status data for Canada and EU-wide |
| 16 | Multiple | Butylone tramadol lethal interaction | 5 | — | Safety-critical interaction flag for editorial review |
| 17 | WebSearch | butylone physical properties melting point solubility CAS 17762-90-2 | 10 | 1 | Physical properties data |
| 18 | WebSearch | Koeppe Ludwig Zeile 1967 synthesis butylone history | 10 | 1 | Historical origin of butylone |
| 19 | PubMed | PMID 32249347 Luethi Liechti designer drugs | 1 | 1 | Authoritative comprehensive review for class-level adverse effects applicable to butylone |
| 20 | Multiple · absence | Butylone stereochemistry enantiomer data | 0 | — | Establishes gap in stereochemistry data for butylone |
| 21 | PubMed | wastewater cathinone prevalence monitoring | 5 | 0 | Establishes that butylone has low population-level prevalence compared to other synthetic cathinones |
| 22 | PubChem/Web | Butylone CID 56843046 physical properties SMILES | 1 | 1 | Chemical identity verification; physical properties |
67 claims by section — every cited sentence, checked against its source
safety16 · 7 ok
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
The Warrick case (combined methylone + butylone serotonin syndrome, death at 48h) and the Rojek case (isolated butylone intentional overdose, blood 20 mg/L, death at ~4h) constitute the complete published human acute toxicity dataset.supported
Case report: 21-year-old male suicide who ingested bk-MBDB (butylone). Blood concentration 20 mg/L; liver concentration 33 mg/kg. Death within ~4 hours of hospitalization. j.forsciint.2012.04.034
The 20 mg/L postmortem blood concentration in the Rojek case is exceptionally high — most cathinone-related fatalities involve blood concentrations below 1 mg/Lsupported
Fatal concentrations rarely exceed 1 mg/L in postmortem fluids. eurrev_201801_14129
Claim in safety — not_supportednot supportedworking →
Elliott and Evans (2014) note that for cathinones generally, blood concentration does not reliably predict outcome.supported
Blood concentration does not predict outcome for fatalities or impairment. bks136
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Roque Bravo et al. (2021) characterized butylone hepatotoxicity in three cell models:partially supported
Hepatotoxicity EC50 1.21 mM for butylone in primary rat hepatocytes. CYP450 inhibition increased butylone toxicity (metabolic activation produces toxic metabolites). Mitochondrial disruption, oxidative stress, apoptosis/necrosis, autophagy. s00204-021-02990-9
In vitro neurotoxicity is demonstrated in differentiated human SH-SY5Y neuroblastoma cells: dose-dependent cell death via ROS production (p < 0.0001), decreased mitochondrial bioenergetics, calcium dysregulation, and caspase 3/7-mediated apoptosissupported
Butylone neurotoxicity in SH-SY5Y: dose-dependent ROS, decreased mitochondrial bioenergetics, Ca2+ increase, caspase 3/7 activation. ijms21041370
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Class-level evidence from animal self-administration studies demonstrates that cathinones with DAT activity support operant responding, with reinforcing efficacy proportional to DAT potency.supported
Rodents self-administer MDPV and methylone intravenously in patterns similar to methamphetamine. Rank order of reinforcing efficacy: MDPV >= methamphetamine > methylone. 209875
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Roque Bravo et al. (2021) demonstrated that CYP450 inhibitors increase butylone hepatotoxicity in vitrosupported
CYP450 inhibition increased butylone toxicity (metabolic activation produces toxic metabolites). s00204-021-02990-9
pharmacology12 · 12 ok
At the dopamine transporter, butylone functions as an uptake inhibitor (blocker) rather than a releasing substrate, placing it in the cocaine-like mechanistic category at this sitesupported
Butylone acts as a DAT blocker and 5-HT transporter substrate, characterizing its mixed stimulant/entactogen profile. s00213-018-5075-5
This is corroborated by Eshleman et al. (2013), who describe butylone as a "lower affinity uptake inhibitor" at human recombinant DAT compared to mephedrone and methylone.supported
Butylone classified as lower affinity uptake inhibitor at DAT, SERT, NET. MDPV and naphyrone: pure uptake inhibitors. Mephedrone, methylone: transporter substrates that induce release. j.bcp.2013.04.004
At the serotonin transporter, butylone acts as a substrate — it is transported into the presynaptic terminal and triggers non-exocytotic serotonin release via transporter reversal, mechanistically analogous to MDMAsupported
Butylone acts as a DAT blocker and 5-HT transporter substrate, characterizing its mixed stimulant/entactogen profile. s00213-018-5075-5
Simmler et al. (2012) confirm that butylone induces 5-HT release in addition to uptake inhibition.supported
Butylone acts as a non-selective monoamine uptake inhibitor similar to cocaine, and also induces 5-HT release similar to MDMA. j.1476-5381.2012.02145.x
Simmler et al. (2012) initially classified butylone as a "non-selective monoamine uptake inhibitor similar to cocaine", while the more recent and mechanistically granular characterization by Saha et al. (2019) resolves the SERT substrate distinctionsupported
Butylone acts as a non-selective monoamine uptake inhibitor similar to cocaine, and also induces 5-HT release similar to MDMA. j.1476-5381.2012.02145.x
Simmler et al. (2012) initially classified butylone as a "non-selective monoamine uptake inhibitor similar to cocaine", while the more recent and mechanistically granular characterization by Saha et al. (2019) resolves the SERT substrate distinctionsupported
Butylone acts as a DAT blocker and 5-HT transporter substrate, characterizing its mixed stimulant/entactogen profile. s00213-018-5075-5
Unlike mephedrone and methylone, it does not robustly release preloaded norepinephrine in superfusion assays.supported
Butylone classified as lower affinity uptake inhibitor at DAT, SERT, NET. Mephedrone, methylone: transporter substrates that induce release. j.bcp.2013.04.004
López-Arnau et al. (2012) demonstrated dose-dependent hyperlocomotion in mice at 5–25 mg/kg i.p., blocked by both ketanserin (5-HT₂A antagonist) and haloperidol (D₂ antagonist)supported
Butylone (5-25 mg/kg) caused hyperlocomotion in mice; inhibited 5-HT and dopamine uptake; affinities for 5-HT2A receptors similar to MDMA. Hyperlocomotion prevented with ketanserin or haloperidol. j.1476-5381.2012.01998.x
Microdialysis data exist for the related cathinones methylone and mephedrone, but direct measurement of butylone's effects on extracellular monoamine concentrations in vivo remains a gap.supported
Methylone and mephedrone are nonselective substrates for monoamine transporters. IV administration increases extracellular DA and 5-HT in rat NAc. npp.2011.304
Uralets et al. (2014) conducted the largest human urinary excretion study for synthetic cathinones, finding that methylenedioxy-substituted cathinones (including butylone) undergo carbonyl reduction to a lesser extent than non-methylenedioxy cathinonessupported
SC with methylenedioxy attachment to aromatic ring (including butylone) metabolize by carbonyl reduction to lesser extent; best detected as parent drug in free urine fraction. bku021
Roque Bravo et al. (2021) confirmed CYP450 involvement in butylone metabolism using selective inhibitors in primary rat hepatocytes, but did not identify the specific CYP isoforms responsiblesupported
CYP450 inhibition increased butylone toxicity (metabolic activation produces toxic metabolites). s00204-021-02990-9
The moderate LogP (1.34) and confirmed high BBB permeability are consistent with rapid CNS penetration.partially supported
High blood-brain barrier permeability in vitro model. j.1476-5381.2012.02145.x
receptor-pharmacology8 · 5 ok
Butylone's affinity at all three monoamine transporters (DAT, SERT, NET) is lower than that of methylone and mephedronesupported
Butylone classified as lower affinity uptake inhibitor at DAT, SERT, NET. Mephedrone, methylone: transporter substrates that induce release. j.bcp.2013.04.004
Its DAT/SERT selectivity ratio places it between methylone (more SERT-selective) and MDPV (highly DAT-selective), in a roughly non-selective range with preferential SERT substrate activity versus DAT blocking activity.supported
Butylone acts as a non-selective monoamine uptake inhibitor similar to cocaine, and also induces 5-HT release similar to MDMA. j.1476-5381.2012.02145.x
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Eshleman et al. (2013) characterized butylone's activity at multiple non-transporter targets using human recombinant receptor systems:supported
Butylone had low potency at hVMAT2, weak 5-HT1A partial agonism, 5-HT2A antagonism. j.bcp.2013.04.004
The 5-HT₂A finding is notable: López-Arnau et al. (2012) demonstrated that ketanserin (5-HT₂A antagonist) blocks butylone's hyperlocomotor effects in vivo, suggesting functional 5-HT₂A engagement despite the in vitro antagonist classificationsupported
Affinities for 5-HT2A receptors similar to MDMA. Hyperlocomotion prevented with ketanserin or haloperidol. j.1476-5381.2012.01998.x
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Simmler et al. (2012) report high BBB permeability for butylone in an in vitro model, consistent with its established CNS psychoactivity despite the β-keto group's general reduction of lipophilicity relative to non-keto analogues.supported
High blood-brain barrier permeability in vitro model. j.1476-5381.2012.02145.x
pharmacokinetic-detail6 · 4 ok
The LogP of 1.34 and confirmed high BBB permeability in vitro predict rapid absorption and CNS penetrationpartially supported
High blood-brain barrier permeability in vitro model. j.1476-5381.2012.02145.x
Uralets et al. (2014) established that butylone, as a methylenedioxy-substituted cathinone, undergoes less carbonyl reduction than non-methylenedioxy cathinonessupported
SC with methylenedioxy attachment to aromatic ring (including butylone) metabolize by carbonyl reduction to lesser extent; best detected as parent drug in free urine fraction. bku021
Roque Bravo et al. (2021) demonstrated CYP450-dependent metabolic activation — not detoxification — in primary rat hepatocytessupported
CYP450 inhibition increased butylone toxicity (metabolic activation produces toxic metabolites). s00204-021-02990-9
These predictions derive from in vitro rat hepatocyte data and have not been confirmed in human clinical settings.supported
Hepatotoxicity EC50 1.21 mM for butylone in primary rat hepatocytes. s00204-021-02990-9
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
comparative-pharmacology5 · 3 ok
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
This table illustrates a systematic shift across the series: as α-alkyl chain length increases, the mechanism transitions from SERT substrate (releaser) to SERT blocker, and DAT selectivity increasessupported
Butylone classified as lower affinity uptake inhibitor at DAT, SERT, NET. Mephedrone, methylone: transporter substrates that induce release. j.bcp.2013.04.004
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Simmler et al. (2012) classified butylone as pharmacologically similar to cocaine (non-selective uptake inhibitor)supported
Butylone acts as a non-selective monoamine uptake inhibitor similar to cocaine. j.1476-5381.2012.02145.x
The comparison is partially apt — both are monoamine uptake inhibitors — but butylone's additional SERT substrate (releasing) activity and absence of local anesthetic (sodium channel blocking) properties distinguish it mechanisticallysupported
Butylone acts as a DAT blocker and 5-HT transporter substrate, characterizing its mixed stimulant/entactogen profile. s00213-018-5075-5
history5 · 4 ok
Claim in history — inconclusiveinconclusiveworking →
A second fatality — an isolated butylone suicide in Poland — was reported by Rojek et al. the same year.supported
Case report: 21-year-old male suicide who ingested bk-MBDB (butylone). Blood concentration 20 mg/L; liver concentration 33 mg/kg. Death within ~4 hours of hospitalization. j.forsciint.2012.04.034
Baumann et al. (2012), in a study co-authored by Alexander Shulgin, characterized the broader class of methylenedioxy cathinones (mephedrone, methylone) as monoamine transporter substrates analogous to MDMA, providing the pharmacological framework within which butylone was subsequently studiedsupported
Methylone and mephedrone are nonselective substrates for monoamine transporters. IV administration increases extracellular DA and 5-HT in rat NAc. npp.2011.304
The first dedicated pharmacology papers appeared in 2012: López-Arnau et al. published comparative neuropharmacology data, and Simmler et al. characterized it as a non-selective uptake inhibitor with serotonin-releasing properties.supported
Butylone (5-25 mg/kg) caused hyperlocomotion in mice; inhibited 5-HT and dopamine uptake; affinities for 5-HT2A receptors similar to MDMA. j.1476-5381.2012.01998.x
The first dedicated pharmacology papers appeared in 2012: López-Arnau et al. published comparative neuropharmacology data, and Simmler et al. characterized it as a non-selective uptake inhibitor with serotonin-releasing properties.supported
Butylone acts as a non-selective monoamine uptake inhibitor similar to cocaine, and also induces 5-HT release similar to MDMA. j.1476-5381.2012.02145.x
summary5 · 5 ok
With an estimated total duration of 3–5 hours oral and moderate potency relative to methylone and mdma, butylone occupies a middle position in the methylenedioxy cathinone series — shorter-acting than MDMA but pharmacologically less potent than methylone at monoamine transporters.partially supported
Butylone classified as lower affinity uptake inhibitor at DAT, SERT, NET. Mephedrone, methylone: transporter substrates that induce release. j.bcp.2013.04.004
Butylone exhibits a dual transporter mechanism: it functions as a dopamine transporter (DAT) blocker (uptake inhibitor) while simultaneously acting as a serotonin transporter (SERT) substrate (releaser)supported
Butylone acts as a DAT blocker and 5-HT transporter substrate, characterizing its mixed stimulant/entactogen profile. s00213-018-5075-5
This mechanistic split — cocaine-like at DAT, MDMA-like at SERT — produces a hybrid stimulant-entactogen phenomenology: increased energy and euphoria from dopaminergic reuptake inhibition, with empathogenic warmth and prosocial effects mediated by serotonin releasesupported
Butylone acts as a non-selective monoamine uptake inhibitor similar to cocaine, and also induces 5-HT release similar to MDMA. j.1476-5381.2012.02145.x
Two human fatalities are documented: one from combined methylone-butylone serotonin syndrome (blood concentration unreported for butylone alone), and one isolated butylone suicide at a blood concentration of 20 mg/Lsupported
Case report of lethal serotonin syndrome after combined methylone and butylone ingestion. s13181-011-0199-6
Two human fatalities are documented: one from combined methylone-butylone serotonin syndrome (blood concentration unreported for butylone alone), and one isolated butylone suicide at a blood concentration of 20 mg/Lsupported
Case report: 21-year-old male suicide who ingested bk-MBDB (butylone). Blood concentration 20 mg/L; liver concentration 33 mg/kg. Death within ~4 hours of hospitalization. j.forsciint.2012.04.034
neuroscience4 · 4 ok
Class-level evidence from synthetic cathinone self-administration studies demonstrates that DAT-active cathinones support operant responding in rodents, with reinforcing efficacy proportional to DAT potencysupported
Rodents self-administer MDPV and methylone intravenously in patterns similar to methamphetamine. Rank order of reinforcing efficacy: MDPV >= methamphetamine > methylone. 209875
Butylone's relatively lower DAT affinity compared to MDPV or mephedrone predicts moderate, not extreme, reinforcing potential.supported
Butylone classified as lower affinity uptake inhibitor at DAT, SERT, NET. MDPV and naphyrone: pure uptake inhibitors. j.bcp.2013.04.004
5-HT₂A activation (indirect, via released 5-HT) — confirmed behaviorally by ketanserin blockade of butylone-induced hyperlocomotionsupported
Hyperlocomotion prevented with ketanserin or haloperidol. j.1476-5381.2012.01998.x
Leong et al. (2020) demonstrated that butylone produces dose-dependent neurotoxicity in differentiated SH-SY5Y (human dopaminergic neuronal) cellssupported
Butylone neurotoxicity in SH-SY5Y: dose-dependent ROS, decreased mitochondrial bioenergetics, Ca2+ increase, caspase 3/7 activation. ijms21041370
clinical-evidence3 · 1 ok
Claim in clinical-evidence — inconclusiveinconclusiveworking →
For context, most cathinone-related fatalities rarely exceed 1 mg/L in postmortem blood, and this case is consistent with massive intentional ingestion rather than typical recreational dosing.supported
Fatal concentrations rarely exceed 1 mg/L in postmortem fluids. eurrev_201801_14129
Claim in clinical-evidence — inconclusiveinconclusiveworking →
chemistry2 · 0 ok
effects-overview1 · 1 ok
Compared to methylone, the experience is similar in character but lower in ceiling intensity, reflecting butylone's reduced affinity at all three monoamine transporters.supported
Butylone classified as lower affinity uptake inhibitor at DAT, SERT, NET. Mephedrone, methylone: transporter substrates that induce release. j.bcp.2013.04.004