generation run 2026-05-07
53 min completedmodel pipeline-v5plan not recordedrun/fb3444f6…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
- sparse_evidence
- structural_inference
- 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
23 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | PubChem | 3-fluoroamphetamine | 1 | 1 | Primary chemical identity verification |
| 2 | PubMed | fluoroamphetamine monoamine releaser dopamine serotonin norepinephrine | 4 | 3 | Core pharmacological characterization and in vivo behavior data for PAL-353 |
| 3 | ClinicalTrials.gov · absence | 3-fluoroamphetamine PAL-353 cocaine | 0 | 0 | No active or completed trials; gap documented |
| 4 | OpenAlex | 3-fluoroamphetamine PAL-353 pharmacology | 3 | 1 | High-citation in vivo pharmacodynamic data with DA and 5-HT microdialysis in rat nucleus accumbens |
| 5 | PubMed | fluoroamphetamine monoamine transporter binding affinity | 1 | 1 | Included as class-level comparator for fluoroamphetamine pharmacology |
| 6 | PubMed | PAL-353 3-fluoroamphetamine cocaine use disorder treatment | 1 | 0 | Duplicate of already-identified paper |
| 7 | PubMed | 3-fluoroamphetamine pharmacology | 3 | 3 | All directly relevant to 3-FA pharmacology, administration, and PK |
| 8 | PubMed | Rothman Baumann PAL-353 amphetamine analog monoamine releaser | 8 | 3 | Additional preclinical behavior and neurochemistry papers using PAL-353 as reference compound |
| 9 | PsychonautWiki | — | 1 | 2 | Community consensus dose/duration data cross-reference |
| 10 | WebSearch | 3-FA 3-fluoroamphetamine DAT NET SERT EC50 release Ki binding affinity transporter | 10 | 1 | Identified EC50 values for DAT and NET; need primary source verification |
| 11 | WebSearch | 3-fluoroamphetamine legal status UK US EU Canada Australia scheduling 2025 | 10 | 2 | Legal status verification for multiple jurisdictions |
| 12 | PubMed | indirect chiral separation amphetamine derivatives GC HPLC psychoactive compounds novel | 1 | 1 | Analytical/forensic chemistry data confirming 3-FA has chiral center; characterization of positional isomers |
| 13 | ClinicalTrials.gov · absence | 3-fluoroamphetamine PAL-353 cocaine | 0 | 0 | Confirmed no clinical trials for 3-FA as of 2026 |
| 14 | PubMed | fluoroamphetamine intoxication death adverse effects heart cardiac | 1 | 1 | Important adverse event/toxicity data for fluoroamphetamine class; establishes cardiovascular and CNS risks |
| 15 | UNODC LSS | — | 1 | 2 | Official chemical identifier verification |
| 16 | PubMed | 4-fluoroamphetamine pharmacokinetics human controlled study oral ingestion | 3 | 2 | Useful comparative PK data for the fluoroamphetamine class; 3-FA has no human PK studies |
| 17 | PubMed | amphetamine trace amine associated receptor TAAR1 agonist psychostimulant monoamine | 4 | 2 | TAAR1 mechanism for amphetamine class; class-level inference for 3-FA |
| 18 | WebSearch | 3-fluoroamphetamine Australia TGA scheduled poison amphetamine analog | 10 | 2 | Australian/NZ legal status |
| 19 | PubMed | stimulant drug overdose treatment emergency management amphetamine toxicity | 3 | 2 | Emergency management protocols for amphetamine-class toxicity - relevant to 3-FA overdose |
| 20 | PMC | PAL-353 EC50 values dopamine norepinephrine serotonin | 1 | 3 | Critical pharmacological data confirming mechanism of action and transporter selectivity |
| 21 | WebSearch | 3-fluoroamphetamine history synthesis research chemical market first appearance | 10 | 2 | Historical context for 3-FA appearance |
| 22 | WebSearch | 3-FA 3-fluoroamphetamine DAT NET SERT EC50 release Ki binding affinity transporter | 10 | 1 | Cross-reference verification of pharmacological data |
| 23 | WebSearch | 3-fluoroamphetamine Canada CDSA controlled drug substances | 10 | 1 | Canadian legal status - unresolved, flagged |
130 claims by section — every cited sentence, checked against its source
pharmacology30 · 2 ok
Claim in pharmacology — inconclusiveinconclusiveworking →
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Anchondo et al. (2025) demonstrated in mice and rats that 3-FA produces locomotor stimulation comparable to methamphetamine (peak locomotor counts: 5905–7758, similar to methamphetamine peak response) and fully substitutes for methamphetamine in drug discrimination with ED₅₀ = 0.32–0.71 mg/kg.supported
3-FA showed peak locomotor effects similar to methamphetamine. All compounds produced time- and dose-dependent locomotor stimulation (ED50 0.38-7.38 mg/kg) and fully substituted for methamphetamine in discriminative stimulus tests (ED50 0.32-0.71 mg/kg). j.jpet.2025.103617
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
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By class analogy with 4-fluoroamphetamine — the closest positional-isomer with published human metabolic data — fluoroamphetamines are expected to undergo beta-hydroxylation (yielding fluorophenylpropanolamines) and aromatic ring hydroxylation followed by glucuronide conjugationsupported
Three metabolites: two diastereomers of 4-fluorophenylpropanolamine and one ring-hydroxylated 4-FA (conjugated). Two metabolic pathways identified. j.jpba.2019.113008
safety18 · 4 ok
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
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Management centers on benzodiazepines as first-line therapy for agitation and seizure threshold protection, active cooling for hyperthermia, and avoidance of beta-blockers (which risk unopposed alpha-adrenergic vasoconstriction). Antipsychotics carry seizure risk and QT prolongation risk and are not preferred first-line agents.supported
Antipsychotics discouraged due to lowered seizure threshold, QT prolongation, and decreased heat dissipation. Benzodiazepines recommended first-line. j.ajem.2019.01.001
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Anchondo et al. (2025) noted that fluorinated amphetamine analogs as a class have been associated with heart failure, cerebral hemorrhage, and death, though these adverse events have been documented primarily for 4-fa — including fatal intoxications involving 4-FA in combination with other substancespartially supported
Six fatalities from combination of 4-FA and 25C-NBOMe over 9 months. Four drug-caused deaths; postmortem 4-FA blood concentrations 330-682 ng/mL. Agitation, seizures, pulmonary/cerebral edema. bkac059
Claim in safety — inconclusiveinconclusiveworking →
The compound's high DA/NE selectivity with minimal serotonin activity means it lacks the self-limiting serotonergic component that reduces reinforcing efficacy in mdma-like compounds — elevated synaptic serotonin attenuates dopaminergic reinforcement, a brake absent in 3-FAsupported
Lower 5-HT:DA ratio = higher reinforcing efficacy. pmid:15677348
Anchondo et al. (2025) concluded that 3-FA's abuse potential is "comparable to that of methamphetamine".supported
Results indicate abuse potential comparable to methamphetamine. j.jpet.2025.103617
Claim in safety — inconclusiveinconclusiveworking →
summary18 · 3 ok
Claim in summary — inconclusiveinconclusiveworking →
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It was investigated as a candidate agonist pharmacotherapy for cocaine use disorder, demonstrating reduced cocaine self-administration in non-human primates and a pharmacokinetic profile suitable for transdermal deliverypartially supported
DA/NE-selective releasers have different cocaine-choice profiles versus serotonergic releasers. fbp.0b013e32834d63ac
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
In rhesus monkey self-administration paradigms, 3-FA maintains positive reinforcement comparable to other dopamine-selective amphetamine analogs, and its abuse potential has been assessed as comparable to methamphetamine. tolerance develops through anticipated dopaminergic downregulation, though no substance-specific tolerance studies have been publishedpartially supported
All analogs positive reinforcers in rhesus monkeys. Lower 5-HT:DA ratio = higher reinforcing efficacy. pmid:15677348
In rhesus monkey self-administration paradigms, 3-FA maintains positive reinforcement comparable to other dopamine-selective amphetamine analogs, and its abuse potential has been assessed as comparable to methamphetamine. tolerance develops through anticipated dopaminergic downregulation, though no substance-specific tolerance studies have been publishedpartially supported
3-FA showed peak locomotor effects similar to methamphetamine. Results indicate abuse potential comparable to methamphetamine. j.jpet.2025.103617
history16 · 0 ok
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clinical-evidence12 · 0 ok
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comparative-pharmacology12 · 2 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 →
In drug discrimination studies, 3-FA fully substitutes for methamphetamine with comparable potency (ED₅₀ = 0.32–0.71 mg/kg)supported
All compounds produced time- and dose-dependent locomotor stimulation (ED50 0.38-7.38 mg/kg) and fully substituted for methamphetamine in discriminative stimulus tests (ED50 0.32-0.71 mg/kg). j.jpet.2025.103617
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Peak locomotor stimulation in mice is equivalent between 3-FA and methamphetamine (5905–7758 counts).supported
3-FA showed peak locomotor effects similar to methamphetamine. j.jpet.2025.103617
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
pharmacokinetic-detail8 · 0 ok
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
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neuroscience6 · 0 ok
Claim in neuroscience — inconclusiveinconclusiveworking →
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chemistry4 · 0 ok
receptor-pharmacology4 · 0 ok
legal-status2 · 1 ok
Claim in legal-status — inconclusiveinconclusiveworking →
3-FA's structural relationship to amphetamine (differing only by a fluorine atom at the meta ring position) and its pharmacological similarity (potent DA/NE releaser with methamphetamine-comparable behavioral effects) make it a strong candidate for prosecution under analogue provisions in jurisdictions that employ themsupported
3-FA showed peak locomotor effects similar to methamphetamine. Results indicate abuse potential comparable to methamphetamine. All compounds fully substituted for methamphetamine in discriminative stimulus tests. j.jpet.2025.103617