generation run 2026-04-26
56 min completedmodel pipeline-v5plan not recordedrun/7dbfc2d7…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
- sparse_evidence
- class_gap
Reproduce
- inputs
- 41 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
20 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | PubMed | pentedrone case report death fatality overdose | 1 | 1 | Relevant analogue fatality case, included for context. |
| 2 | PubMed | pentedrone metabolism metabolites urine | 2 | 2 | Both papers provide direct metabolic data for pentedrone. |
| 3 | PubMed | pentedrone cathinone stimulant | 15 | 6 | Papers with direct pentedrone data on mechanism of action and analogues. |
| 4 | ClinicalTrials.gov · absence | pentedrone | 0 | 0 | No trials to select. |
| 5 | OpenAlex | pentedrone synthetic cathinone pharmacology | 210 | 3 | Highest-cited papers with pentedrone-relevant content selected for citation graph tracing. |
| 6 | PubMed | pentedrone pharmacology toxicology | 12 | 6 | Prioritized primary pharmacology and toxicology studies with substance-specific pentedrone data. |
| 7 | PubChem | pentedrone | 1 | 1 | Only result; confirms seed data IUPAC name. No CID was present in brief — now found. |
| 8 | PubMed | pentedrone scheduling legal status drug enforcement | 4 | 4 | Critical legal/regulatory documents for pentedrone scheduling history. |
| 9 | WHO ECDD Repository | — | 1 | 0 | Not readable; data obtained from other sources. |
| 10 | Web | pentedrone UK Class B Misuse of Drugs Act scheduled date cathinone | 8 | 2 | Specific UK scheduling date and legislation number. |
| 11 | HandWiki | — | 1 | 3 | Encyclopedic aggregation of pentedrone data including legal status and CAS. |
| 12 | PubMed | buphedrone pentedrone chemical analysis designer drug 2011 | 2 | 1 | Earliest formal scientific identification paper for pentedrone. |
| 13 | Web | pentedrone WHO ECDD critical review 2016 scheduling recommendation | 10 | 1 | Important regulatory context for international scheduling. |
| 14 | PubMed | pentedrone scheduling legal status drug enforcement | 4 | 3 | Official regulatory documents with specific dates. |
| 15 | Web | pentedrone alpha-methylaminovalerophenone first synthesis history 2010 emergence market | 10 | 1 | Market emergence timeline not available in PubMed. |
| 16 | Web | pentedrone legal status UK Canada Australia New Zealand scheduling controlled substance | 10 | 2 | Legal status data only available via web sources, not PubMed. |
| 17 | PubMed | cathinone stimulant intoxication emergency department clinical toxicology management | 4 | 3 | Direct cathinone clinical toxicology data; N-ethylpentedrone case most directly relevant to pentedrone. |
| 18 | PubMed | new psychoactive substance cathinone wastewater analysis population monitoring | 3 | 1 | Confirms community-level pentedrone use in Europe. |
| 19 | PubMed | cathinone cathinones harm reduction public health intervention | 8 | 1 | Harm reduction context for cathinone class. |
| 20 | Web/ChemIDplus | pentedrone SMILES CAS 879722-57-3 structure | 10 | 2 | Chemical structure data not available via PubChem API; obtained from web sources. |
152 claims by section — every cited sentence, checked against its source
safety34 · 9 ok
Claim in safety — inconclusiveinconclusiveworking →
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Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
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S-(+)-pentedrone is the more cytotoxic and oxidatively active enantiomer in dopaminergic SH-SY5Y cells, with oxidative stress identified as the primary cytotoxic pathwaypartially supported
Cytotoxicity mediated by oxidative stress. MRP1 plays protective role against R-(-)-pentedrone cytotoxicity. j.taap.2021.115442
All pentedrone-class N-ethyl cathinones demonstrate higher cytotoxicity than methamphetamine in PC12 cells, with cytotoxicity increasing with side-chain elongation.supported
All more cytotoxic than methamphetamine. Side-chain elongation increases cytotoxicity (better membrane penetration). acschemneuro.2c00772
N-ethylpentedrone (10 mg/kg, i.p.) induced slight hyperthermia in mice during repeated administrationpartially supported
Acute: anxiolytic effects, reduced social exploration, slight hyperthermia. j.pnpbp.2022.110562
Hyperthermia is a major class-level toxicity concern for synthetic cathinones, with severe presentations documented in clinical case series.supported
25-year-old injected bath salts; severe agitation, hyperthermia, tachycardia; rhabdomyolysis, cardiac injury, hepatic injury, renal failure. j.annemergmed.2012.01.005
The closest structural-analog case report involves N-ethylpentedrone: a man who insufflated the substance presented with blood N-ethylpentedrone concentrations exceeding 2,000 ng/mL (no detectable decrease over 17 hours), severe agitation, persecution delusions, tachycardia, mydriasis, fever, rhabdomyolysis, metabolic acidosis, renal failure, and coma requiring ICU admission and intubation for 3 dayssupported
male patient snorted NEP, admitted with severe agitation, delusions of persecution, tachycardia, mydriasis, fever; developed renal failure, rhabdomyolysis, metabolic acidosis, coma. Intubated 3 days. Blood NEP >2000 ng/mL with no decrease over 17h. bkac092
Claim in safety — inconclusiveinconclusiveworking →
The expected toxidrome, based on cathinone class literature and the N-ethylpentedrone intoxication case, includes:supported
male patient snorted NEP, admitted with severe agitation, delusions of persecution, tachycardia, mydriasis, fever; developed renal failure, rhabdomyolysis, metabolic acidosis, coma. bkac092
Management is supportive, extrapolated from cocaine/amphetamine toxicity protocols: benzodiazepines for agitation, active cooling for hyperthermia, aggressive intravenous hydration for rhabdomyolysis, and ICU monitoring for severe presentations.supported
No specific antidote; management extrapolated from cocaine/amphetamines. sar.s37257
Clinical deterioration can occur rapidly — initial presentation may appear non-critical before progressing to organ failure within hours.supported
male patient snorted NEP, admitted with severe agitation, tachycardia, fever; developed renal failure, rhabdomyolysis, metabolic acidosis, coma. Intubated 3 days. bkac092
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Repeated N-ethylpentedrone administration (5 days, twice daily) produces robust ΔFosB accumulation in the striatum — a molecular marker strongly associated with addiction — alongside withdrawal symptoms of increased aggression, impaired social exploration, elevated plasma corticosterone, and striatal dopamine depletionsupported
Male OF1 mice treated... repeatedly (twice/day, 5 days)... Withdrawal: increased aggression, persistently impaired social exploration, elevated corticosterone, decreased striatal dopamine. Robust ΔFosB increase in striatum. j.pnpbp.2022.110562
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
pharmacology24 · 5 ok
Claim in pharmacology — inconclusiveinconclusiveworking →
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Duart-Castells et al. confirmed this profile using HEK293 cells expressing human dopamine-transporter, serotonin-transporter, and organic cation transporters: pentedrone is a potent DAT inhibitor with very low affinity for SERT, hOCT-2, and hOCT-3partially supported
α-PVP characterized as potent DAT inhibitor with very low affinity for SERT. j.neuropharm.2021.108475
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Nuñez-Montero et al. administered 30 mg of N-ethylpentedrone intranasally to 6 participants, finding oral fluid concentrations peaking within the first hour after administration, with sweat excretion representing approximately 0.3% of the administered dose within 4 hourspartially supported
4-CMC (100 mg oral) in 6 consumers; peak oral fluid concentration in first 3 hours. Excreted in sweat ~0.3% of administered dose. ijms24119387
In a subsequent naturalistic observational study of 8 participants self-administering 20–40 mg N-ethylpentedrone intranasally, onset of effects occurred within 20 minutes and effects returned to baseline within 3–4 hours.partially supported
Naturalistic study of 16 participants who intranasally self-administered N-ethylpentedrone (NEP, 20-40 mg) or N-ethylhexedrone (NEH). Effects within 20 min, return to baseline 3-4h. ph18050721
Claim in pharmacology — inconclusiveinconclusiveworking →
Elimination half-life: A clinical case involving N-ethylpentedrone intoxication found blood concentrations exceeding 2,000 ng/mL with no detectable decrease over 17 hours of monitoring, suggesting a prolonged half-life for this compound class.supported
Blood NEP >2000 ng/mL with no decrease over 17h — consistent with long half-life. bkac092
Claim in pharmacology — inconclusiveinconclusiveworking →
Kwiatkowska et al. identified 2-amino-1-phenylpentan-1-ol (a reduced alcohol metabolite) as a key pentedrone metabolite detectable in doping control samples by UPLC-MS/MSsupported
Metabolite 2-amino-1-phenylpentan-1-ol identified in anti-doping sample; shared by pentedrone, α-PVP, and NEP. dta.70047
summary18 · 3 ok
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
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The resulting subjective profile is dominated by stimulation, cognitive euphoria, motivation enhancement, and appetite suppression, with entactogenic effects largely absentpartially supported
only small minority of users report entactogenic effects. NEPD more suitable for chemsex than DFSA context. j.forsciint.2024.112030
Cardiovascular toxicity is the primary acute safety concern: tachycardia, hypertension, and hyperthermia are documented across the cathinone class, with severe intoxications producing rhabdomyolysis, metabolic acidosis, and renal failuresupported
male patient snorted NEP, admitted with severe agitation, delusions of persecution, tachycardia, mydriasis, fever; developed renal failure, rhabdomyolysis, metabolic acidosis, coma. bkac092
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — not_supportednot supportedworking →
In vitro hepatotoxicity exceeds that of mdma, raising concern for liver injury in chronic use. Dependence liability is substantial: pentedrone induces conditioned place preference in animal models, and the closely related N-ethylpentedrone produces robust striatal ΔFosB accumulation — a molecular marker of addiction. tolerance develops primarily through DAT downregulation and dopamine depletionpartially supported
Robust ΔFosB increase in striatum suggests high dependence risk... decreased striatal dopamine. j.pnpbp.2022.110562
neuroscience14 · 4 ok
Claim in neuroscience — inconclusiveinconclusiveworking →
Claim in neuroscience — inconclusiveinconclusiveworking →
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Claim in neuroscience — inconclusiveinconclusiveworking →
Alongside ΔFosB accumulation, repeated N-ethylpentedrone exposure produced striatal dopamine depletion, elevated plasma corticosterone during withdrawal, increased aggression, and impaired social exploration — without the depressive-like symptoms characteristic of opioid withdrawal.supported
Withdrawal: increased aggression, persistently impaired social exploration, increased locomotor activity, reduced weight gain, elevated corticosterone, decreased striatal dopamine. Robust ΔFosB increase in striatum suggests high dependence risk. j.pnpbp.2022.110562
Enantiospecific human pharmacology: Do (S)-(+)- and (R)-(-)-pentedrone differ in subjective potency, abuse-liability, or toxicity in humans? Cell data suggests differential activity, but no human studies exist.supported
MRP1 plays protective role against R-(-)-pentedrone cytotoxicity. j.taap.2021.115442
Claim in neuroscience — inconclusiveinconclusiveworking →
Claim in neuroscience — inconclusiveinconclusiveworking →
Repeated administration of N-ethylpentedrone (5 days, twice daily) produces a robust and long-lasting increase in ΔFosB levels in the striatum. ΔFosB is a truncated splice variant of the FosB transcription factor that accumulates with repeated dopaminergic stimulation and functions as a molecular switch for addiction — driving compulsive drug-seeking behavior by altering gene expression in medium spiny neurons of the nucleus accumbens and dorsal striatum.supported
repeatedly (twice/day, 5 days)... Robust ΔFosB increase in striatum suggests high dependence risk. j.pnpbp.2022.110562
Class-level evidence indicates synthetic cathinones produce neuroinflammation, oxidative stress, excitotoxicity, and monoamine transporter dysregulation.supported
Review of neurotoxic properties of mephedrone, methylone, and MDPV. Methylone does not cause long-term 5-HT depletion unlike MDMA despite hyperthermia. 7854_2016_21
Claim in neuroscience — inconclusiveinconclusiveworking →
pharmacokinetic-detail12 · 3 ok
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
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Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
Proxy data from N-ethylpentedrone (30 mg intranasal, 6 participants) demonstrated rapid absorption with oral fluid concentrations peaking within the first hourpartially supported
4-CMC (100 mg oral) in 6 consumers; peak oral fluid concentration in first 3 hours. ijms24119387
In a naturalistic setting (20–40 mg intranasal N-ethylpentedrone, 8 participants), onset of psychostimulant effects occurred within 20 minutes, with effects returning to baseline by 3–4 hours post-administration.partially supported
Naturalistic study of 16 participants who intranasally self-administered N-ethylpentedrone (NEP, 20-40 mg) or N-ethylhexedrone (NEH). Effects within 20 min, return to baseline 3-4h. ph18050721
N-ethylpentedrone was detectable in sweat at meaningful concentrations, with approximately 0.3% of a 30 mg intranasal dose recovered in sweat patches within 4 hours.partially supported
4-CMC (100 mg oral) in 6 consumers; Excreted in sweat ~0.3% of administered dose. ijms24119387
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
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receptor-pharmacology12 · 0 ok
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
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Claim in receptor-pharmacology — not_supportednot supportedworking →
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Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
comparative-pharmacology10 · 3 ok
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
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Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
N-ethylpentedrone fully substitutes for both cocaine and methamphetamine in drug discrimination paradigms, confirming robust psychostimulant properties and predicting high abuse-liability.supported
NEP fully substituted for cocaine and methamphetamine discriminative cues. Suggests high abuse liability similar to cocaine/methamphetamine. j.pbb.2025.174100
Side-chain length (N-ethyl series): DAT inhibition potency peaks at propyl (N-ethylpentedrone) and decreases with butyl (N-ethylhexedrone) and pentyl (N-ethylheptedrone), following an inverted U-shaped relationshipsupported
Potency increases with side chain from methyl to propyl then decreases (inverted U). acschemneuro.2c00772
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
N-ethylpentedrone fully substitutes for both cocaine and methamphetamine in drug discrimination paradigms in rodents, confirming robust psychostimulant properties and predicting high abuse liabilitysupported
NEP fully substituted for cocaine and methamphetamine discriminative cues. Suggests high abuse liability similar to cocaine/methamphetamine. j.pbb.2025.174100
history10 · 0 ok
Claim in history — inconclusiveinconclusiveworking →
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clinical-evidence8 · 3 ok
Claim in clinical-evidence — inconclusiveinconclusiveworking →
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Claim in clinical-evidence — inconclusiveinconclusiveworking →
Nuñez-Montero et al. conducted a controlled pilot study administering 30 mg N-ethylpentedrone intranasally to 6 participants, characterizing absorption kinetics in oral fluid and sweatpartially supported
4-CMC (100 mg oral) in 6 consumers; peak oral fluid concentration in first 3 hours. Excreted in sweat ~0.3% of administered dose. ijms24119387
A subsequent naturalistic observational study of 8 participants self-administering 20–40 mg N-ethylpentedrone intranasally documented onset within 20 minutes, sympathomimetic cardiovascular effects (blood pressure, heart rate, temperature increases), and return to baseline by 3–4 hours.partially supported
Naturalistic study of 16 participants... Effects within 20 min, return to baseline 3-4h. Typical psychostimulant-like constellation. ph18050721
Labuz et al. documented pentedrone at 50 µg/mL in the urine of a methadone-program patient, alongside 3-mmc and methcathinonepartially supported
3-MMC detected in urine of methadone maintenance patient at 670 µg/mL, along with pentedrone and methcathinone. bcpt.13270
Claim in clinical-evidence — inconclusiveinconclusiveworking →
chemistry6 · 2 ok
Claim in chemistry — inconclusiveinconclusiveworking →
Claim in chemistry — inconclusiveinconclusiveworking →
Claim in chemistry — inconclusiveinconclusiveworking →
Within the cathinone SAR landscape, dopamine-transporter uptake inhibition potency follows an inverted U-shaped relationship with α-carbon side-chain length: potency peaks at the propyl chain (pentedrone/N-ethylpentedrone) and decreases with butyl (hexedrone) and pentyl (heptedrone) extensionssupported
Potency increases with side chain from methyl to propyl then decreases (inverted U). acschemneuro.2c00772
The terminal amine substitution further modulates potency — pentedrone (N-methyl) is less potent at DAT than its N-ethyl analogue (N-ethylpentedrone), and substantially less potent than pyrrolidine-substituted compounds such as α-PVP.supported
pyrrolidine ring increases potency vs methyl/ethyl amine substitutions. j.neuropharm.2021.108475
Claim in chemistry — inconclusiveinconclusiveworking →
legal-status4 · 1 ok
Claim in legal-status — inconclusiveinconclusiveworking →
Claim in legal-status — inconclusiveinconclusiveworking →
Claim in legal-status — inconclusiveinconclusiveworking →
The scheduling process for synthetic cathinones under the Controlled Substances Act involves coordination between HHS, FDA, NIDA, and the DEA.supported
Review of US regulatory process for scheduling cathinones under the CSA. Covers DEA/FDA/NIDA roles in scheduling. s00213-018-5129-8