generation run 2026-05-03
93 min completedmodel pipeline-v5plan not recordedrun/5689394b…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
none raised on this run
Reproduce
- inputs
- 21 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 | PubMed | DOB-dragonfly benzo difuran phenethylamine synthesis | 1 | 1 | Key SAR paper for the DragonFLY ring system |
| 2 | ClinicalTrials.gov · absence | Bromo-DragonFLY | 0 | — | No trials to select |
| 3 | WebSearch | bromo-dragonfly fatality case report Sweden Norway ischemia amputation | 10 | 3 | Primary toxicity case documentation |
| 4 | PubChem | Bromo-DragonFLY by name | 1 | 1 | Confirmed chemical identity data for brief verification |
| 5 | WebSearch | Bromo-DragonFLY synthesis history Matthew Parker Nichols 1998 MAPS | 10 | 3 | Confirmed synthesis history; leads to specific PMID 9857084 |
| 6 | PubMed | Halberstadt FLY DragonFLY phenylalkylamine hallucinogen behavioral head twitch | 1 | 1 | Key in vivo potency data with direct Bromo-DragonFLY measurements |
| 7 | OpenAlex | Bromo-DragonFLY psychedelic phenethylamine | 49 | 2 | Corazza 2011 is the primary dedicated review of Bromo-DragonFLY; Luethi 2020 is landmark NPS review |
| 8 | Tennessee Poison Center website | Bromo-DragonFLY clinical data | 1 | 1 | Clinical overview from poison center |
| 9 | PubMed | Bromo-DragonFLY pharmacology toxicology | 2 | 2 | Both directly characterize Bromo-DragonFLY receptor pharmacology |
| 10 | PubMed | 2C-B-FLY benzodifuran receptor binding hallucinogen potency | 1 | 1 | Explains extraordinary duration; critical pharmacokinetics finding |
| 11 | PubMed | novel (benzodifuranyl)aminoalkane extremely potent 5-HT2A receptor 1998 | 1 | 1 | Original synthesis and pharmacology paper for Bromo-DragonFLY |
| 12 | WebSearch | O'Connor 2014 Bromo-DragonFLY synthesis Drug Testing Analysis DOI | 10 | 3 | Synthesis chemistry and comprehensive ADME predictions |
| 13 | PubChem REST API | — | 1 | 4 | Confirmed chemical identity data missing from brief |
| 14 | WebSearch | Andreasen Muller bromo-dragonfly fatal poisoning forensic journal 2009 | 10 | 2 | Both are key toxicological case reports with analytical data |
| 15 | Multiple sources | Tramadol + Bromo-DragonFLY interaction mechanism | 2 | 2 | Establishes mechanistic basis for dangerous tramadol interaction in brief |
| 16 | WebSearch | Bromo-DragonFLY UK legal status scheduling 2009 2010 | 10 | 2 | Critical legal and harm reduction context |
| 17 | PubMed | ADME bromo-dragonfly in silico 2025 | 1 | 1 | Most recent ADME data; important discrepancy with Noble 2018 |
| 18 | PubMed | PMID 19876858 | 1 | 1 | Key clinical case report of Bromo-DragonFLY toxicity |
71 claims by section — every cited sentence, checked against its source
safety22 · 14 ok
The only published single-drug fatal case documented a femoral blood concentration of 4.7 ng/g in an 18-year-old woman with no other drugs detectedsupported
18-year-old woman, fatal overdose. Femoral blood 0.0047 mg/kg. No other drugs detected. j.forsciint.2008.11.001
Claim in safety — inconclusiveinconclusiveworking →
No human LD₅₀ or therapeutic index has been established. In silico modeling predicts significant acute toxicity with notable species variation, but no human-equivalent LD₅₀ value has been computed.supported
Significant acute toxicity with species variation in LD50. acs.chemrestox.4c00105
Claim in safety — inconclusiveinconclusiveworking →
The multi-day duration due to metabolic resistance and concurrent MAO-A inhibition maintaining elevated serotonin tone create a sustained vasoconstrictive insult without precedent among psychedelic compounds.supported
Long duration (2-3 days) explained by metabolic resistance. MAO-A inhibition Ki = 0.352 microM (competitive). j.toxlet.2018.07.018
The multi-day duration due to metabolic resistance and concurrent MAO-A inhibition maintaining elevated serotonin tone create a sustained vasoconstrictive insult without precedent among psychedelic compounds.supported
Long duration (2-3 days) explained by metabolic resistance. MAO-A inhibition Ki = 0.352 microM (competitive). j.toxlet.2018.07.018
In silico modeling predicts notable hERG channel inhibition, suggesting an additional cardiac arrhythmia risk beyond vasoconstrictionsupported
Notable cardiotoxicity risk via hERG channel inhibition. acs.chemrestox.4c00105
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
De la Fuente Revenga et al. demonstrated in mouse head-twitch response assays that tolerance to 5-HT₂A-mediated behavior develops within a single administration, driven by 5-HT₂A receptor downregulation in frontal cortex via a β-arrestin-2-independent mechanism.supported
Tolerance develops rapidly (within single dose) to HTR. Mechanism involves 5-HT2AR downregulation, independent of beta-arrestin-2. acschemneuro.2c00170
Cross-tolerance with other serotonergic 5-HT₂A agonists (LSD, psilocin, mescaline, DOB) is pharmacologically predicted based on the shared receptor target and confirmed bidirectional cross-tolerance between DOI and LSD in the same assaysupported
Cross-tolerance between psychedelic 5-HT2AR agonists (DOI, LSD) but not with non-psychedelic lisuride. acschemneuro.2c00170
The interaction profile of Bromo-DragonFLY is dominated by two pharmacological features: potent 5-HT₂A agonism and competitive MAO-A inhibition (Ki = 0.352 µM)supported
MAO-A inhibition Ki = 0.352 microM (competitive). j.toxlet.2018.07.018
Tramadol is a serotonin-norepinephrine reuptake inhibitor with weak μ-opioid activity; co-administration with an MAO-A inhibitor creates a well-established pharmacological pathway to serotonin syndromesupported
MAO-A inhibition Ki = 0.352 microM (competitive). j.toxlet.2018.07.018
Tramadol is a serotonin-norepinephrine reuptake inhibitor with weak μ-opioid activity; co-administration with an MAO-A inhibitor creates a well-established pharmacological pathway to serotonin syndromesupported
Tramadol induces serotonin syndrome-like behaviors, exaggerated in SERT-deficient mice. MAOIs + tramadol dangerous combination. s146114570900011x
Fox et al. demonstrated in SERT-deficient mice that tramadol produces exaggerated serotonin syndrome behaviors and explicitly cautioned against concurrent MAOI usesupported
Tramadol induces serotonin syndrome-like behaviors, exaggerated in SERT-deficient mice. MAOIs + tramadol dangerous combination. s146114570900011x
Predicted hERG channel inhibition adds cardiac arrhythmia risk for individuals with long QT syndrome or other cardiac conduction abnormalities.supported
Notable cardiotoxicity risk via hERG channel inhibition. acs.chemrestox.4c00105
Concurrent serotonergic medications — including SSRIs, SNRIs, MAOIs, triptans, tramadol, and St. John's wort — are contraindicated due to the compound's MAO-A inhibitory activity and the resulting risk of serotonin syndrome.supported
MAO-A inhibition Ki = 0.352 microM (competitive). j.toxlet.2018.07.018
Hepatic impairment — while the compound shows no hepatic metabolism in vitro, acute liver failure has been documented in overdose cases, suggesting direct hepatotoxicity at high exposures.partially supported
Bromo-dragonfly resistant to hepatic metabolism in HLM/HLC in vitro. j.toxlet.2018.07.018
Claim in safety — inconclusiveinconclusiveworking →
pharmacology12 · 10 ok
Bromo-DragonFLY is a potent, multi-target serotonin receptor agonist whose primary psychedelic effects are mediated through 5-HT₂A receptor activation. Åstrand et al. screened 60 new psychoactive substances and found Bromo-DragonFLY exhibited the highest 5-HT₂A potency of all compounds tested (EC₅₀ = 0.05 nM), approximately 400 times more potent than LSD at this receptorsupported
Bromo-dragonfly showed highest 5-HT2A potency of 60 NPS tested: EC50 = 0.05 nM, 400x more potent than LSD. j.forsciint.2020.110553
The benzodifuran ring system is responsible for this exceptional potency: incorporation of the methoxy groups into aromatic furan rings confers an approximately 27-fold increase in 5-HT₂A affinity compared to the non-rigid positional isomer, and in vivo head-twitch response assays confirm a 3.75-fold potency enhancement over DOB (ED₅₀ = 0.20 µmol/kg versus 0.75 µmol/kg).partially supported
Benzodifuran ring system showed ~27-fold increase in 5-HT2A affinity vs non-rigid positional isomer. pmid:12113827
The benzodifuran ring system is responsible for this exceptional potency: incorporation of the methoxy groups into aromatic furan rings confers an approximately 27-fold increase in 5-HT₂A affinity compared to the non-rigid positional isomer, and in vivo head-twitch response assays confirm a 3.75-fold potency enhancement over DOB (ED₅₀ = 0.20 µmol/kg versus 0.75 µmol/kg).supported
DOB-DFLY (Bromo-DragonFLY) ED50 = 0.20 umol/kg vs DOB 0.75 umol/kg (3.75x more potent). Benzodifuran ring system confers potency enhancement. j.neuropharm.2018.10.037
Bromo-DragonFLY was the only compound among 60 NPS tested that activated all four receptors screened: μ-opioid, CB₁, 5-HT₁A, and 5-HT₂Asupported
Only compound to activate all four receptors (mu-opioid, CB1, 5-HT1A, 5-HT2A). j.forsciint.2020.110553
A critical secondary pharmacological activity is competitive inhibition of MAO-A (Ki = 0.352 µM; IC₅₀ ≈ 540 nM)partially supported
MAO-A inhibition Ki = 0.352 microM (competitive). j.toxlet.2018.07.018
Claim in pharmacology — inconclusiveinconclusiveworking →
Noble et al. tested the compound in pooled human liver microsomes (HLM) and pooled human liver cytosol (HLC) and found no metabolism in either systemsupported
Bromo-dragonfly resistant to hepatic metabolism in HLM/HLC in vitro. j.toxlet.2018.07.018
Notably, MAO-A does not metabolize Bromo-DragonFLY — the compound inhibits MAO-A rather than serving as its substrate.supported
2C-B-FLY metabolised by CYP2D6 and MAO-A but bromo-dragonfly is not. MAO-A inhibition Ki = 0.352 microM (competitive). j.toxlet.2018.07.018
In silico predictions by Noga and Jurowski suggest CYP450-mediated metabolism (epoxidation, quinone formation, UGT conjugation, N-dealkylation) and primarily renal excretionsupported
Multiple CYP450 involved in metabolism. Metabolites via epoxidation, quinone formation, UGT conjugation, N-dealkylation. Renal excretion primary. s41598-025-06453-4
This contradicts the direct experimental finding of no hepatic metabolism; the discrepancy likely reflects limitations of computational prediction versus observed metabolic behavior, though extrahepatic pathways not captured by the HLM/HLC assay cannot be excluded.supported
Bromo-dragonfly resistant to hepatic metabolism in HLM/HLC in vitro. j.toxlet.2018.07.018
Claim in pharmacology — inconclusiveinconclusiveworking →
Plasma protein binding was measured by Noble et al. but the specific value is not available from the published abstract. In silico modeling predicts high gastrointestinal absorption, blood-brain barrier penetration, and significant plasma protein binding.supported
High GI absorption, BBB penetration predicted. Significant plasma protein binding. s41598-025-06453-4
summary7 · 5 ok
This extraordinary duration reflects near-complete resistance to hepatic metabolism.supported
Long duration (2-3 days) explained by metabolic resistance. j.toxlet.2018.07.018
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Bromo-DragonFLY exhibits exceptional 5-HT₂A receptor potency (EC₅₀ = 0.05 nM, approximately 400-fold greater than LSD) and activates 5-HT₂B, 5-HT₂C, 5-HT₁A, μ-opioid, and CB₁ receptorspartially supported
EC50 = 0.05 nM, 400x more potent than LSD. Only compound to activate all four receptors (mu-opioid, CB1, 5-HT1A, 5-HT2A). j.forsciint.2020.110553
Competitive inhibition of MAO-A (Ki = 0.352 µM) potentiates serotonin accumulation in vivo, contributing to both the prolonged duration and the dangerous interaction profile with serotonergic drugs.supported
MAO-A inhibition Ki = 0.352 microM (competitive). Long duration (2-3 days) explained by metabolic resistance. j.toxlet.2018.07.018
Bromo-DragonFLY presents critical acute toxicity risk: a narrow and poorly characterized dose-response window, sustained peripheral vasoconstriction mediated through α₁-adrenergic and 5-HT₂B agonism that has resulted in gangrene and limb amputation, and predicted hERG channel inhibition suggesting cardiac arrhythmia potentialpartially supported
Significant acute toxicity with species variation in LD50. Notable cardiotoxicity risk via hERG channel inhibition. acs.chemrestox.4c00105
Tolerance arises rapidly through 5-HT₂A receptor downregulation in frontal cortex, with cross-tolerance expected across serotonergic psychedelicssupported
Tolerance develops rapidly (within single dose) to HTR. Mechanism involves 5-HT2AR downregulation. Cross-tolerance between psychedelic 5-HT2AR agonists (DOI, LSD) but not with non-psychedelic lisuride. acschemneuro.2c00170
pharmacokinetic-detail6 · 5 ok
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
Noble et al. demonstrated no detectable biotransformation in pooled human liver microsomes or pooled human liver cytosol, in direct contrast to the structurally related 2C-B-FLY, which is metabolized by CYP2D6 (monohydroxylation, N-acetylation) and by MAO-A (aldehyde metabolite)supported
Bromo-dragonfly resistant to hepatic metabolism in HLM/HLC in vitro. 2C-B-FLY metabolised by CYP2D6 and MAO-A but bromo-dragonfly is not. j.toxlet.2018.07.018
Other FLY-class compounds (2C-E-FLY, 2C-EF-FLY, 2C-T-7-FLY) also undergo hepatic metabolism, further demonstrating that Bromo-DragonFLY's metabolic resistance is specific to its molecular structure rather than a class property.supported
FLY series metabolism via CYP2D6, 3A4, FMO3, NAT1/2, MAO-A/B. Main steps: hydroxylation and N-acetylation. Contextualizes bromo-dragonfly metabolic resistance by contrast. dta.2675
No in vivo human pharmacokinetic parameters have been published. In silico predictions suggest high gastrointestinal absorption, blood-brain barrier penetration, and significant plasma protein bindingsupported
High GI absorption, BBB penetration predicted. Significant plasma protein binding. s41598-025-06453-4
<div class="compact-kv"> <table> <tbody> <tr><td>Oral bioavailability</td><td>Not determined (predicted high in silico)</td></tr> <tr><td>Tmax</td><td>Not determined</td></tr> <tr><td>Plasma half-life</td><td>Not determined</td></tr> <tr><td>Volume of distribution</td><td>Not determined</td></tr> <tr><td>Protein binding</td><td>Measured but unreported in abstract</td></tr> <tr><td>Hepatic metabolism</td><td>None detected (HLM/HLC)</td></tr> <tr><td>MAO-A metabolism</td><td>None (compound inhibits MAO-A instead)</td></tr> <tr><td>Predicted excretion</td><td>Renal (in silico)</td></tr> </tbody> </table> </div>supported
Bromo-dragonfly resistant to hepatic metabolism in HLM/HLC in vitro. MAO-A inhibition Ki = 0.352 microM (competitive). 2C-B-FLY metabolised by CYP2D6 and MAO-A but bromo-dragonfly is not. j.toxlet.2018.07.018
<div class="compact-kv"> <table> <tbody> <tr><td>Oral bioavailability</td><td>Not determined (predicted high in silico)</td></tr> <tr><td>Tmax</td><td>Not determined</td></tr> <tr><td>Plasma half-life</td><td>Not determined</td></tr> <tr><td>Volume of distribution</td><td>Not determined</td></tr> <tr><td>Protein binding</td><td>Measured but unreported in abstract</td></tr> <tr><td>Hepatic metabolism</td><td>None detected (HLM/HLC)</td></tr> <tr><td>MAO-A metabolism</td><td>None (compound inhibits MAO-A instead)</td></tr> <tr><td>Predicted excretion</td><td>Renal (in silico)</td></tr> </tbody> </table> </div>supported
Bromo-dragonfly resistant to hepatic metabolism in HLM/HLC in vitro. MAO-A inhibition Ki = 0.352 microM (competitive). j.toxlet.2018.07.018
chemistry5 · 3 ok
The parent scaffold is the benzo[1,2-b;4,5-b']difuran ring system — a planar tricyclic structure formed by incorporating both methoxy oxygen atoms of 2,5-dimethoxyphenethylamines into fused aromatic furan ringssupported
Benzodifuran ring system showed ~27-fold increase in 5-HT2A affinity vs non-rigid positional isomer. Foundational SAR for DragonFLY class. pmid:12113827
Claim in chemistry — inconclusiveinconclusiveworking →
The compound is the 4-bromo derivative of this scaffold, carrying an α-methyl group on the aminoalkyl side chain (making it an amphetamine analog), and is formally designated as the rigid cyclized analog of DOB.supported
DOB-DFLY (Bromo-DragonFLY) ED50 = 0.20 umol/kg vs DOB 0.75 umol/kg. Benzodifuran ring system confers potency enhancement; alpha-methyl group also contributes. j.neuropharm.2018.10.037
Claim in chemistry — not_supportednot supportedworking →
No published characterization of the melting point, solubility, partition coefficient (log P), or salt forms of Bromo-DragonFLY exists in the retrieved literature. In silico modeling predicts high gastrointestinal absorption, blood-brain barrier penetration, and significant plasma protein binding, consistent with the compound's lipophilic benzodifuran scaffoldsupported
High GI absorption, BBB penetration predicted. Significant plasma protein binding. s41598-025-06453-4
comparative-pharmacology5 · 5 ok
This conformational restriction produces quantifiable potency enhancement: Halberstadt et al. demonstrated a 3.75-fold lower ED₅₀ in the mouse head-twitch response assay (0.20 µmol/kg versus 0.75 µmol/kg for DOB)supported
DOB-DFLY (Bromo-DragonFLY) ED50 = 0.20 umol/kg vs DOB 0.75 umol/kg (3.75x more potent). j.neuropharm.2018.10.037
Chambers et al. measured an approximately 27-fold increase in 5-HT₂A binding affinity for the benzodifuran scaffoldsupported
Benzodifuran ring system showed ~27-fold increase in 5-HT2A affinity vs non-rigid positional isomer. pmid:12113827
The discrepancy between the in vitro affinity enhancement (~27×) and in vivo potency enhancement (~3.75×) likely reflects pharmacokinetic differences, including the drastically different metabolic profiles of the two compounds — DOB undergoes hepatic metabolism, while Bromo-DragonFLY does not.supported
Bromo-dragonfly resistant to hepatic metabolism in HLM/HLC in vitro. j.toxlet.2018.07.018
Rickli et al. characterized 2C-B-FLY's pharmacology as indicating "predominant hallucinogenic properties and a risk for vasoconstriction" — a characterization that applies with greater force to Bromo-DragonFLYsupported
2C-B-FLY (benzodifuran) very potently interacted with 5-HT2 receptors and TAAR1. Indicates predominant hallucinogenic properties and risk for vasoconstriction. bph.13128
At the 5-HT₂A receptor, Bromo-DragonFLY is approximately 400 times more potent than LSD by EC₅₀ (0.05 nM versus ~20 nM)supported
EC50 = 0.05 nM, 400x more potent than LSD. j.forsciint.2020.110553
history4 · 2 ok
Claim in history — inconclusiveinconclusiveworking →
The parent compound DOB (2,5-dimethoxy-4-bromoamphetamine) had been first synthesized by Alexander Shulgin in 1973; Bromo-DragonFLY represents its rigid cyclized analog, incorporating both methoxy oxygen atoms into aromatic furan rings of the benzo[1,2-b;4,5-b']difuran nucleussupported
DOI, DOC, DOB all first synthesized 1973. acsptsci.4c00157
In 2009, Andreasen et al. published the first forensic case report with analytical quantification — an 18-year-old Danish woman found dead, with Bromo-DragonFLY confirmed as the sole cause of death at a femoral blood concentration of 4.7 ng/g.supported
First report of quantification of Bromo-DragonFLY in a deceased person. 18-year-old woman, fatal overdose. Femoral blood 0.0047 mg/kg. No other drugs detected. j.forsciint.2008.11.001
Claim in history — inconclusiveinconclusiveworking →
clinical-evidence3 · 1 ok
Andreasen et al. documented the death of an 18-year-old woman found dead with Bromo-DragonFLY confirmed as the sole cause of deathsupported
18-year-old woman, fatal overdose. No other drugs detected. j.forsciint.2008.11.001
Claim in clinical-evidence — inconclusiveinconclusiveworking →
Claim in clinical-evidence — inconclusiveinconclusiveworking →
neuroscience3 · 3 ok
As a potent 5-HT₂A agonist, Bromo-DragonFLY is expected to produce its psychedelic effects through activation of 5-HT₂A receptors on layer V pyramidal neurons in the prefrontal cortex — the same cellular trigger established for LSD, psilocybin, and DOBsupported
Benzodifuran ring system confers potency enhancement. Potency in mice parallels human hallucinogenic data. j.neuropharm.2018.10.037
The compound's additional 5-HT₁A agonism may modulate these effects, as 5-HT₁A activation has been shown to attenuate some 5-HT₂A-mediated responses in other psychedelic systems.supported
Only compound to activate all four receptors (mu-opioid, CB1, 5-HT1A, 5-HT2A). j.forsciint.2020.110553
The μ-opioid and CB₁ receptor activation unique to Bromo-DragonFLY among tested NPS may introduce phenomenological features not present in pure serotonergic psychedelics — potentially including analgesic, anxiolytic, or reward-circuit components — though no published study has isolated these contributions.supported
Only compound to activate all four receptors (mu-opioid, CB1, 5-HT1A, 5-HT2A). j.forsciint.2020.110553
receptor-pharmacology3 · 2 ok
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
These Ki ranges derive from aggregated published studies; direct verification of the range endpoints against original binding assay publications is pending.supported
MAO-A inhibition Ki = 0.352 microM (competitive). j.toxlet.2018.07.018
The compound produced markedly different response profiles in the two systems, suggesting functional bias, though the calculated bias factor approximated zerosupported
Bromo-DragonFLY showed markedly different responses in beta-arrestin 2 vs miniGalphaq bioassays suggesting biased agonism, though calculated bias factor approx 0. j.bcp.2020.114251
effects-overview1 · 0 ok
Claim in effects-overview — inconclusiveinconclusiveworking →