generation run 2026-05-08
65 min completedmodel pipeline-v5plan not recordedrun/4ae0b0d4…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
- sparse_evidence
- structural_inference
- safety_data_unverified
Reproduce
- inputs
- 25 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 | Web | acetylfentanyl potency morphine fentanyl comparison ED50 LD50 | 10 | 2 | Specific pharmacological parameters not available via API |
| 2 | PubMed | acetylfentanyl Rhode Island outbreak public health deaths 2013 | 1 | 1 | Critical historical paper on first US outbreak |
| 3 | PubMed | acetylfentanyl misuse novel synthetic opioids Prekupec review | 1 | 1 | Key review with epidemiological death counts and naloxone guidance |
| 4 | PubMed | acetylfentanyl pharmacology opioid receptor | 5 | 4 | Core pharmacology and receptor activity data |
| 5 | OpenAlex | acetylfentanyl fentanyl analog opioid pharmacology | 10 | 5 | Landmark reviews most relevant to acetylfentanyl pharmacology, metabolism, and epidemiology |
| 6 | PubMed | acetylfentanyl overdose death toxicology | 15 | 10 | Epidemiology, overdose concentrations, case reports for toxicity section |
| 7 | Web search / EUDA | acetylfentanyl legal status UK Canada Australia EU scheduling | 10 | 1 | European legal status and fatality data |
| 8 | ClinicalTrials.gov · absence | acetylfentanyl | 0 | 0 | No trials - confirmed acetylfentanyl has no approved medical use or clinical development |
| 9 | PubChem | acetylfentanyl | 1 | 1 | Primary chemical identity verification |
| 10 | PubMed | acetylfentanyl metabolism hepatocytes CYP | 1 | 1 | Specific acetylfentanyl metabolism data |
| 11 | Federal Register / DEA | acetylfentanyl DEA Schedule I scheduling date | 1 | 1 | Primary US legal scheduling source |
| 12 | Web / Gov.uk | acetylfentanyl UK Misuse of Drugs Act Class A | 1 | 1 | UK legal status - unresolved/flag for review |
| 13 | Multiple sources | acetylfentanyl blood concentration fatal vs non-fatal comparison | 5 | 1 | Verify seed dose/toxicity data and establish fatal concentration ranges |
| 14 | PubMed / Federal Register | DEA Schedule I final order acetylfentanyl 2017 | 1 | 1 | Primary legal source for US Schedule I status |
| 15 | Web / PMC | acetylfentanyl potency ED50 LD50 therapeutic index | 1 | 1 | Key source for potency data and historical context |
| 16 | Web / Canada.ca | acetylfentanyl Canada CDSA schedule fentanyl analog | 1 | 1 | Canadian legal status |
| 17 | Web / DEA drug info sheet | acetylfentanyl pharmacological data ED50 LD50 therapeutic index | 1 | 0 | Pharmacological parameters from DEA document; could not extract directly from PDF |
| 18 | Web | acetylfentanyl first synthesized Janssen history 1960s | 10 | 1 | Synthesis history data |
75 claims by section — every cited sentence, checked against its source
safety22 · 18 ok
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
This has been confirmed across multiple case series.supported
First major US public health report on acetylfentanyl. 14 overdose deaths in Rhode Island, March-May 2013. Key early outbreak report. s13181-015-0477-9
This has been confirmed across multiple case series.supported
CDC surveillance of opioid overdose deaths; acetylfentanyl identified in >10% of opioid overdose deaths in some states; confirmed acetylfentanyl as one of the most frequently detected fentanyl analogs. mmwr.mm6643e1
This has been confirmed across multiple case series.supported
41 overdose deaths associated with acetylfentanyl in Pennsylvania 2015-2016. 1556-4029.13517
Single-agent fatalities: approximately 250–270 ng/mL peripheral bloodsupported
Acetylfentanyl peripheral blood 260 ng/mL. Cause of death: acute acetylfentanyl intoxication. No other drugs detected. bkv043
Single-agent fatalities: approximately 250–270 ng/mL peripheral bloodsupported
Blood concentration 270 ng/mL. j.legalmed.2016.05.006
Polysubstance fatalities: 0.13–2100 ng/mLsupported
Blood acetylfentanyl concentrations: range 0.13–2100 ng/mL, median 11 ng/mL. 96% multiple drug toxicities. 1556-4029.13517
Claim in safety — inconclusiveinconclusiveworking →
Pennsylvania series (n=41): median 11 ng/mL, mean 169.3 ng/mL; 96% involved multiple drugssupported
41 overdose deaths associated with acetylfentanyl in Pennsylvania 2015-2016. Blood acetylfentanyl concentrations: range 0.13–2100 ng/mL, median 11 ng/mL. 96% multiple drug toxicities. 1556-4029.13517
Impaired driving (living subjects): 1.0–9.2 ng/mLsupported
Acetylfentanyl always co-detected with fentanyl; blood concentrations 1.0–9.2 ng/mL. bkab085
The extreme variability in fatal concentrations reflects the dominant role of co-intoxicants, individual opioid tolerance, and postmortem redistribution artifacts.supported
Review of postmortem toxicology of synthetic opioids. Covers acetylfentanyl: tissue concentration ranges, postmortem redistribution, pharmacokinetic parameters, stability. fphar.2018.01210
Postmortem distribution studies demonstrate that brain tissue accumulates the highest concentrations, followed by blood and vitreous humor, consistent with high lipophilicity and preferential CNS sequestration.supported
Highest concentrations in brain > blood > vitreous humor. j.forsciint.2019.109999
The clinical presentation in documented cases uniformly involves loss of consciousness and deep sedation, precluding assessment of acute psychological effects at sub-sedating doses from published forensic data.supported
Opioid toxidrome: loss of consciousness, bradypnea, hypercapnia, hypotension, miosis. 15563650.2018.1554187
The clinical presentation in documented cases uniformly involves loss of consciousness and deep sedation, precluding assessment of acute psychological effects at sub-sedating doses from published forensic data.supported
NSOs including acetylfentanyl cause classic opioid toxidrome reversible by naloxone. adm.0000000000000324
The DEA permanently scheduled acetylfentanyl in Schedule I partly on the basis of its high potential for abusesupported
Final order maintaining acetylfentanyl in Schedule I CSA, including isomers, esters, ethers, salts. pmid:28591974
Maitland and colleagues specifically investigated the reinforcing properties of fentanyl analogs including acetylfentanyl in the context of illicit drug market substancessupported
There is little information about the reinforcing effects of clandestine fentanyl analogs (FAs). s00213-024-06641-6
This mechanism accounts for the majority of documented acetylfentanyl fatalities: 96% of deaths in the Pennsylvania series involved multiple drugs.supported
96% multiple drug toxicities. 1556-4029.13517
Documented in multiple polysubstance fatality series.supported
41 overdose deaths associated with acetylfentanyl in Pennsylvania 2015-2016. 96% multiple drug toxicities. 1556-4029.13517
A documented fatality involved alprazolam at toxic concentration (64.9 µg/L) alongside acetylfentanyl (32.9 µg/L) and fentanyl.supported
Acetylfentanyl 32.9 μg/L, fentanyl 34.7 μg/L, alprazolam 64.9 μg/L. 1925362119892005
Claim in safety — not_supportednot supportedworking →
Concurrent CNS depressant use: Co-administration with benzodiazepines, alcohol, GHB/GBL, barbiturates, or other opioids carries lethal synergistic respiratory depression risk, as documented in case series.supported
41 overdose deaths associated with acetylfentanyl in Pennsylvania 2015-2016. 96% multiple drug toxicities. 1556-4029.13517
history11 · 3 ok
Between March and May 2013, 14 overdose deaths in Rhode Island, United States, were attributed to acetylfentanyl — the first major outbreak documented in the published literaturesupported
First major US public health report on acetylfentanyl. 14 overdose deaths in Rhode Island, March-May 2013. Key early outbreak report. s13181-015-0477-9
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
Claim in history — not_supportednot supportedworking →
Analysis of the Detroit metropolitan area showed that earlier cases (2015–2016) presented acetylfentanyl as the primary or co-primary intoxicant with mean blood concentrations of 8.9 ng/mL, whereas later cases (2016–2017) showed it predominantly as a minor component alongside fentanyl, with mean concentrations of only 0.9 ng/mLsupported
2016-2017 Detroit deaths: mean acetylfentanyl 0.9 ng/mL; 2015-2016 cohort: mean 8.9 ng/mL acetylfentanyl. Trend shift toward fentanyl-primary with acetylfentanyl artifact of manufacture. 1556-4029.13840
Claim in history — inconclusiveinconclusiveworking →
By 2017, 52 confirmed acetylfentanyl deaths had been documented in the United States since 2013supported
52 acetylfentanyl deaths in US since 2013. adm.0000000000000324
pharmacology11 · 8 ok
Acetylfentanyl is a full agonist at the mu-opioid receptor (MOR), the primary molecular target responsible for its analgesic, euphoric, and respiratory depressant effectssupported
Comprehensive review of novel synthetic opioids including fentanyl analogs. Covers pharmacological properties, patterns of use, desired/unwanted effects, fatal and non-fatal intoxications. fpsyt.2017.00110
Acetylfentanyl is a full agonist at the mu-opioid receptor (MOR), the primary molecular target responsible for its analgesic, euphoric, and respiratory depressant effectssupported
NSOs including acetylfentanyl cause classic opioid toxidrome reversible by naloxone. adm.0000000000000324
Cell-based assay data established a rank order of MOR agonistic activity among fentanyl analogs: fentanyl > isobutyrylfentanyl ≈ butyrylfentanyl ≈ methoxyacetylfentanyl > acetylfentanylsupported
Agonistic activity of fentanyl analogs on μ-opioid receptor via cell-based assay. Rank: fentanyl > isobutyrylfentanyl ≈ butyrylfentanyl ≈ methoxyacetylfentanyl > acetylfentanyl. bpb.b20-00780
A subsequent study confirmed that this rank order extended to the compounds' metabolites.supported
Study measuring agonistic activity of fentanyl analogs and metabolites on opioid receptors using cell-based assay. Acetylfentanyl rank: fentanyl > isobutyrylfentanyl ≈ butyrylfentanyl ≈ methoxyacetylfentanyl > acetylfentanyl. s11419-021-00602-w
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Postmortem distribution studies demonstrate that brain tissue accumulates higher concentrations than peripheral blood or vitreous humor, consistent with preferential CNS sequestrationsupported
Postmortem distribution of synthetic opioids in 58 NYC-OCME cases; acetylfentanyl detected; highest concentrations in brain > blood > vitreous humor. j.forsciint.2019.109999
Metabolism: A liver-humanized mouse study using PXB-cells (hepatocytes from chimeric humanized-liver mice) directly characterized acetylfentanyl's metabolic pathwayssupported
Liver-humanized mouse hepatocytes used to characterize acetylfentanyl metabolism; predictive model for human in vivo metabolism. s11419-018-0425-x
The general metabolic scheme reviewed for fentanyl analogs applies:supported
Systematic review of metabolic profiles of new fentanyl analogs. Metabolism involves hydrolysis, hydroxylation, N/O-dealkylation, O-methylation, and phase II glucuronide/sulfate conjugation. fphar.2019.00238
Claim in pharmacology — inconclusiveinconclusiveworking →
Analytical stability: Acetylfentanyl is stable in blood specimens for up to 9 months under refrigerated (4°C) and room-temperature storage conditions, distinguishing it from less stable analogs such as acryloylfentanylsupported
Validated method and stability study for 13 fentanyl analogs in blood; acetylfentanyl stable under refrigerated/room temp conditions for 9 months. bkab051
pharmacokinetic-detail8 · 7 ok
Single-agent fatalities: approximately 250–270 ng/mL peripheral bloodsupported
Acetylfentanyl peripheral blood 260 ng/mL, central blood 250 ng/mL. Cause of death: acute acetylfentanyl intoxication. bkv043
Single-agent fatalities: approximately 250–270 ng/mL peripheral bloodsupported
Blood concentration 270 ng/mL. j.legalmed.2016.05.006
Polysubstance fatalities: 0.13–2100 ng/mL, reflecting co-intoxicant effects and tolerance variabilitysupported
Blood acetylfentanyl concentrations: range 0.13–2100 ng/mL, median 11 ng/mL. 96% multiple drug toxicities. 1556-4029.13517
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
Brain concentrations of acetylfentanyl exceeded those in peripheral blood and vitreous humor, consistent with the high lipophilicity characteristic of the anilidopiperidine classsupported
Highest concentrations in brain > blood > vitreous humor. j.forsciint.2019.109999
Postmortem redistribution from central to peripheral blood compartments has been documented, complicating interpretation of postmortem blood concentrations.supported
Covers acetylfentanyl: tissue concentration ranges, postmortem redistribution, pharmacokinetic parameters, stability. fphar.2018.01210
The most species-relevant metabolic characterization was conducted using PXB-cells — hepatocytes isolated from liver-humanized chimeric micesupported
Liver-humanized mouse hepatocytes used to characterize acetylfentanyl metabolism; predictive model for human in vivo metabolism. s11419-018-0425-x
Major Phase I metabolic pathways include acetamide bond hydrolysis (yielding 4-ANPP), N-dealkylation (yielding nor-acetylfentanyl), and hydroxylation at piperidine and phenyl ring positionssupported
Metabolism involves hydrolysis, hydroxylation, N/O-dealkylation, O-methylation, and phase II glucuronide/sulfate conjugation. fphar.2019.00238
summary7 · 3 ok
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
It appeared on illicit drug markets in 2012–2013, initially sold as a "research chemical," and rapidly generated public health concern after 14 overdose deaths in Rhode Island between March and May 2013supported
First major US public health report on acetylfentanyl. 14 overdose deaths in Rhode Island, March-May 2013. Key early outbreak report. s13181-015-0477-9
Acetylfentanyl acts as a full agonist at the mu-opioid receptor, producing the classical opioid effect constellation: analgesia, sedation, euphoria, anxiolysis, and dose-dependent respiratory depressionsupported
Comprehensive review of novel synthetic opioids including fentanyl analogs. Covers pharmacological properties, patterns of use, desired/unwanted effects, fatal and non-fatal intoxications. fpsyt.2017.00110
Acetylfentanyl acts as a full agonist at the mu-opioid receptor, producing the classical opioid effect constellation: analgesia, sedation, euphoria, anxiolysis, and dose-dependent respiratory depressionsupported
NSOs including acetylfentanyl cause classic opioid toxidrome reversible by naloxone. adm.0000000000000324
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
comparative-pharmacology4 · 2 ok
Cell-based MOR functional assays rank acetylfentanyl at the lower end of the anilidopiperidine potency spectrum: fentanyl > isobutyrylfentanyl ≈ butyrylfentanyl ≈ methoxyacetylfentanyl > acetylfentanylsupported
Rank: fentanyl > isobutyrylfentanyl ≈ butyrylfentanyl ≈ methoxyacetylfentanyl > acetylfentanyl. bpb.b20-00780
Cell-based MOR functional assays rank acetylfentanyl at the lower end of the anilidopiperidine potency spectrum: fentanyl > isobutyrylfentanyl ≈ butyrylfentanyl ≈ methoxyacetylfentanyl > acetylfentanylsupported
Acetylfentanyl rank: fentanyl > isobutyrylfentanyl ≈ butyrylfentanyl ≈ methoxyacetylfentanyl > acetylfentanyl. s11419-021-00602-w
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
chemistry3 · 1 ok
Claim in chemistry — inconclusiveinconclusiveworking →
Claim in chemistry — inconclusiveinconclusiveworking →
As an anilidopiperidine, acetylfentanyl exhibits high lipophilicity — a class property that enables rapid blood-brain barrier penetration and significant CNS accumulation, as confirmed by postmortem distribution studies showing brain concentrations exceeding those in peripheral blood.supported
Highest concentrations in brain > blood > vitreous humor. j.forsciint.2019.109999
clinical-evidence3 · 3 ok
The compound has no approved medical indication in any jurisdiction and was permanently placed in DEA Schedule I in 2017, a classification that designates the substance as having no currently accepted medical use.supported
Final order maintaining acetylfentanyl in Schedule I CSA, including isomers, esters, ethers, salts. pmid:28591974
All available human data derive from poisoning case reports, postmortem toxicology, and impaired driving analyses.supported
Retrospective study of 270 impaired driving cases (2017–2019) positive for fentanyl, carfentanil, or acetylfentanyl. bkab085
All available human data derive from poisoning case reports, postmortem toxicology, and impaired driving analyses.supported
41 overdose deaths associated with acetylfentanyl in Pennsylvania 2015-2016. Blood acetylfentanyl concentrations. 1556-4029.13517
receptor-pharmacology3 · 3 ok
The rank order of MOR activity was: fentanyl > isobutyrylfentanyl ≈ butyrylfentanyl ≈ methoxyacetylfentanyl > acetylfentanylsupported
Rank: fentanyl > isobutyrylfentanyl ≈ butyrylfentanyl ≈ methoxyacetylfentanyl > acetylfentanyl. bpb.b20-00780
A follow-up study extended this rank order to the metabolites of these compoundssupported
Study measuring agonistic activity of fentanyl analogs and metabolites on opioid receptors. s11419-021-00602-w
A structure-activity relationship study across the N-acyl chain length series (acetylfentanyl → fentanyl → butyrylfentanyl → valerylfentanyl) demonstrated that the rank order of potencies for respiratory depression (hypoventilation) diverges from the rank order for antinociceptionsupported
SAR study of 17 fentanyl-related substances including acetylfentanyl. Acetylfentanyl among the series evaluated for antinociception and hypoventilation in mice. Rank order of potencies for hypoventilation established. j.pbb.2023.173572
neuroscience2 · 2 ok
Postmortem distribution data showing preferential brain accumulation of acetylfentanyl relative to blood and vitreous humor confirm the compound's high CNS partitioning, consistent with the rapid onset of central effects observed clinically.supported
Highest concentrations in brain > blood > vitreous humor. j.forsciint.2019.109999
Does the divergence between antinociceptive and respiratory depressant potency rank orders within the N-acyl series reflect biased agonism at MOR (differential G-protein vs. beta-arrestin signaling), or pharmacokinetic differences in brainstem vs. spinal cord drug delivery?supported
SAR study of 17 fentanyl-related substances including acetylfentanyl. Evaluated for antinociception and hypoventilation in mice. Rank order of potencies for hypoventilation established across N-acyl chain length series. j.pbb.2023.173572
legal-status1 · 0 ok
Claim in legal-status — inconclusiveinconclusiveworking →