generation run 2026-04-28
55 min completedmodel pipeline-v5plan not recordedrun/a3ef542f…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
- sparse_evidence
- no_taper_protocol
Reproduce
- inputs
- 17 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
19 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | PubMed | 3-FPM fluorophenmetrazine analytical forensic detection mass spectrometry | 2 | 2 | Both are primary forensic/toxicology data sources for 3-FPM blood concentrations and postmortem distribution |
| 2 | ClinicalTrials.gov · absence | 3-fluorophenmetrazine phenylmorpholine stimulant | 0 | — | Confirms no clinical trial data available |
| 3 | PubChem | 3-FPM | 1 | 1 | Primary chemical identity verification |
| 4 | PubMed | fluorophenylmorpholine novel psychoactive substance stimulant | 15 | — | None selected - too general, did not return 3-FPM specific results |
| 5 | PubMed | 3-FPM 3-fluorophenmetrazine phenylmorpholine stimulant | 1 | 1 | Directly relevant to 3-FPM market history and isomer pharmacology |
| 6 | OpenAlex | 3-fluorophenmetrazine 3-FPM monoamine transporter stimulant (citations sort) | 9 | 3 | 26810957 is the first characterization paper for 3-FPM; 27552699 mentions 3-FPM in UK NPS context; 32249347 is high-citation designer drug review |
| 7 | PubMed | 3-fluorophenmetrazine dopamine norepinephrine transporter release | 2 | 1 | Mayer et al. is the first published pharmacological characterization of 3-FPM mechanism |
| 8 | PMC | — | 1 | 1 | Severe adverse event case demonstrating extreme vasoconstriction |
| 9 | PMC | — | 1 | 1 | Case report of CNS-depressant combination risk |
| 10 | PubMed | 3-fluorophenmetrazine metabolism CYP isoenzymes Mardal | 1 | 1 | Definitive metabolism/CYP characterization paper |
| 11 | UNODC | — | 1 | 1 | SMILES not returned by PubChem API; UNODC confirmed it |
| 12 | PubMed | PMID 30784204 | 1 | 1 | Only human PK data for 3-FPM |
| 13 | WebSearch | 3-FPM 3-fluorophenmetrazine Sweden Germany UK scheduled controlled | 10 | 1 | Legal status across key jurisdictions |
| 14 | PubMed | 3-fluorophenmetrazine STRIDA Swedish adverse events | 1 | 1 | Clinical adverse events case series from surveillance project |
| 15 | WebSearch | 3-FPM 3-fluorophenmetrazine Sweden Germany UK scheduled controlled 2016 | 10 | 1 | Core legal status information for major jurisdictions |
| 16 | PubMed | phenmetrazine morpholine dopamine releasing stimulant dependence abuse potential | 4 | 1 | Documents parent compound abuse potential via DA/NE releasing mechanism |
| 17 | WebSearch | 3-fluorophenmetrazine PAL-593 patent 2011 phenylmorpholine synthesis | 10 | 1 | First scientific description of 3-FPM; establishes 2011 as synthesis origin point |
| 18 | WebSearch | 3-fluorophenmetrazine CAS number free base melting point physical properties | 10 | 2 | Chemical identity data not available from API tools |
| 19 | OpenAlex | phenmetrazine monoamine releaser dopamine abuse potential (citations sort) | 8 | 1 | Documents phenmetrazine withdrawal history as relevant parent compound context |
70 claims by section — every cited sentence, checked against its source
safety19 · 13 ok
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Intravenous administration produced atrial fibrillation and catastrophic peripheral vasospasm with four-limb ischaemia, culminating in bilateral below-knee amputations and digit necrosissupported
52-year-old male IV user of 3-FPM developed AKI, four-limb ischaemia with atrial fibrillation, hypotension, livedo reticularis. Required bilateral below-knee amputations. s13730-017-0263-4
Widespread T-wave inversions — indicating myocardial repolarization disturbance — were observed on day 5 in a 3-FPM/etizolam overdose case and resolved spontaneously.partially supported
Developed seizure-like activity, T-wave inversions (resolved). bcr-2018-224995
Acute kidney injury requiring 26 days of continuous veno-venous haemofiltration was documented in the intravenous use case, likely secondary to vasospasm-induced renal hypoperfusion and complement activation (C3 0.67 g/L, C4 0.11 g/L).supported
Required bilateral below-knee amputations and prolonged CVVH (26 days). Low complement C3/C4. s13730-017-0263-4
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Phenmetrazine self-administers in rodents at reinforcing doses and produces discriminative stimulus effects in rhesus monkeys that generalize to amphetaminepartially supported
Phenmetrazine (parent compound of 3-FPM) attenuates cocaine self-administration in rodents via DA/NE release. Establishes phenmetrazine abuse liability and dopaminergic mechanism. s00213-015-3875-4
Phenmetrazine self-administers in rodents at reinforcing doses and produces discriminative stimulus effects in rhesus monkeys that generalize to amphetaminesupported
Drug discrimination studies in rhesus monkeys. Establishes phenmetrazine's pharmacological profile and abuse potential. j.drugalcdep.2012.10.026
Chronic phenmetrazine treatment attenuates cocaine self-administration in rats, a finding consistent with cross-tolerance at shared DAT targets.supported
Phenmetrazine (parent compound of 3-FPM) attenuates cocaine self-administration in rodents via DA/NE release. s00213-015-3875-4
Phentermine-class sympathomimetics — pharmacologically analogous to 3-FPM — should be discontinued before surgery due to potential interactions with tramadol and antidepressantssupported
Sympathomimetic anti-obesity medications should be discontinued pre-operatively; potential interactions with tramadol and antidepressants noted for phentermine-class sympathomimetics. pmid:16119498
Multiple published fatalities and near-fatalities involved 3-FPM co-administered with opioids and/or benzodiazepinessupported
Poly-drug death with U-47700, amitriptyline, methamphetamine, diazepam, flubromazolam, delorazepam. bkx060
Multiple published fatalities and near-fatalities involved 3-FPM co-administered with opioids and/or benzodiazepinessupported
Organ distribution of diclazepam, pyrazolam and 3-fluorophenmetrazine. Cause of death: positional asphyxia from poly-drug intoxication. j.forsciint.2019.109959
Multiple published fatalities and near-fatalities involved 3-FPM co-administered with opioids and/or benzodiazepinessupported
Found with empty etizolam 50mg and 3-FPM 500mg packages. bcr-2018-224995
Claim in safety — inconclusiveinconclusiveworking →
Pre-existing cardiovascular disease (hypertension, arrhythmias, coronary artery disease, structural heart disease) — catecholamine surge increases myocardial oxygen demand, heart rate, and blood pressure. The documented cases of tachycardia (47%) and atrial fibrillation support this contraindication.supported
52-year-old male IV user of 3-FPM developed AKI, four-limb ischaemia with atrial fibrillation, hypotension, livedo reticularis. s13730-017-0263-4
Claim in safety — inconclusiveinconclusiveworking →
Concurrent tramadol use — seizure and serotonin syndrome risk.supported
Potential interactions with tramadol and antidepressants noted for phentermine-class sympathomimetics. pmid:16119498
Peripheral vascular disease — the documented case of catastrophic limb ischaemia following intravenous 3-FPM indicates that pre-existing vascular compromise dramatically increases ischaemic risk.supported
Highlights severe vasoconstrictive and end-organ effects. s13730-017-0263-4
pharmacology11 · 10 ok
Claim in pharmacology — not_supportednot supportedworking →
3-FPM is a substrate-type monoamine releasing agent acting at plasma membrane transporters of the SLC6 familysupported
FPM isomers act as monoamine releasers via DAT, NET, SERT in HEK293 cells and rat brain synaptosomes. j.neuropharm.2017.10.006
In HEK293 cells expressing human transporters and rat brain synaptosomes, 3-FPM inhibits uptake at DAT and NET with IC₅₀ values below 2.5 µM (comparable to cocaine), while serotonin transporter (SERT) inhibition is weak (IC₅₀ > 80 µM)supported
2-, 3- and 4-FPM inhibit uptake at DAT and NET with IC50 < 2.5 uM (comparable to cocaine), SERT IC50 > 80 uM. FPM isomers act as monoamine releasers via DAT, NET, SERT in HEK293 cells and rat brain synaptosomes. j.neuropharm.2017.10.006
Each fluorinated phenmetrazine isomer (2-FPM, 3-FPM, 4-FPM) evokes concentration-dependent monoamine release from rat brain synaptosomes, confirming substrate-type releasing activity rather than simple reuptake inhibitionsupported
FPM isomers act as monoamine releasers via DAT, NET, SERT in HEK293 cells and rat brain synaptosomes. j.neuropharm.2017.10.006
The Mayer et al. 2018 study represented the first published pharmacological characterization of 3-FPM's mechanism of actionsupported
First published pharmacological characterization of 3-FPM mechanism of action. j.neuropharm.2017.10.006
No published in vivo pharmacodynamic data exist for 3-FPM in rodents or humans beyond a single pharmacokinetic self-experiment.supported
PK self-experiment: Cmax 210 ng/mL at tmax 2.5 h after oral ingestion. T1/2 ~8.8 h. dta.2577
The only published human pharmacokinetic data derive from Grumann et al. 2019 — a controlled n=1 self-experiment using a single oral dose:supported
PK self-experiment: Cmax 210 ng/mL at tmax 2.5 h after oral ingestion. dta.2577
Excretion is primarily as unchanged compound, with the N-oxide as the principal metabolitepartially supported
Mainly excreted unchanged. Metabolic pathways: aryl-hydroxylation, N-hydroxylation. dta.2577
The oxidative ring-opening product 2-amino-1-(3-fluorophenyl)propan-1-ol showed the longest detection window across all matrices and may serve as the optimal forensic biomarker.supported
Ring-opening product (2-amino-1-(3-fluorophenyl)propan-1-ol) showed largest detection window. dta.2577
Mardal et al. 2016 characterized 3-FPM metabolism using in vivo rat and human urine samples and in vitro CYP isoenzyme studies:supported
Studies on in vivo metabolism in rat and human, in vitro metabolism in human CYP isoenzymes and microbial biotransformation. j.jpba.2016.06.011
While CYP isoenzyme involvement was characterized in vitro, the specific isoenzymes responsible (e.g., CYP2D6, CYP3A4, CYP2B6) are not reported in the published abstractsupported
CYP isoenzyme contributions to phase I metabolism characterized. j.jpba.2016.06.011
summary9 · 9 ok
2-(3-Fluorophenyl)-3-methylmorpholine (3-FPM, PAL-593) is a synthetic phenylmorpholine stimulant and structural analog of phenmetrazine, the anorectic withdrawn from clinical use in the 1980s. 3-FPM occupies a moderate-potency position among catecholamine-releasing stimulants, with dopamine and norepinephrine transporter uptake inhibition IC₅₀ values below 2.5 µM — comparable to cocaine — but weak serotonergic activity (SERT IC₅₀ > 80 µM)supported
2-, 3- and 4-FPM inhibit uptake at DAT and NET with IC50 < 2.5 uM (comparable to cocaine), SERT IC50 > 80 uM. j.neuropharm.2017.10.006
Oral duration spans 4–6 hours, with an elimination half-life of approximately 8.8 hours.partially supported
T1/2 ~8.8 h, Vd ~400 L (5.3 L/kg). dta.2577
The pharmacological evidence base is sparse: one in vitro transporter study, one n=1 human pharmacokinetic self-experiment, one metabolism study, and a handful of clinical toxicology case reports constitute the entirety of published datasupported
First published pharmacological characterization of 3-FPM mechanism of action. j.neuropharm.2017.10.006
The pharmacological evidence base is sparse: one in vitro transporter study, one n=1 human pharmacokinetic self-experiment, one metabolism study, and a handful of clinical toxicology case reports constitute the entirety of published datasupported
PK self-experiment: Cmax 210 ng/mL at tmax 2.5 h after oral ingestion. dta.2577
The pharmacological evidence base is sparse: one in vitro transporter study, one n=1 human pharmacokinetic self-experiment, one metabolism study, and a handful of clinical toxicology case reports constitute the entirety of published datasupported
Main metabolic pathways: N-oxidation, aryl hydroxylation + O-methylation, alkyl hydroxylation, oxidative ring opening yielding bis-dealkylated metabolite, glucuronidation and sulfation. j.jpba.2016.06.011
3-FPM functions as a substrate-type monoamine releasing agent at SLC6-family transporters, entering nerve terminals via DAT and NET to drive carrier-mediated efflux of dopamine and norepinephrinesupported
FPM isomers act as monoamine releasers via DAT, NET, SERT in HEK293 cells and rat brain synaptosomes. j.neuropharm.2017.10.006
Tachycardia occurs in 47% of clinical intoxication presentations, and one intravenous use case produced critical limb ischaemia requiring bilateral below-knee amputationpartially supported
Required bilateral below-knee amputations and prolonged CVVH (26 days). s13730-017-0263-4
All published fatalities involved polysubstance combinationssupported
Poly-drug death with U-47700, amitriptyline, methamphetamine, diazepam, flubromazolam, delorazepam. bkx060
Tolerance and dependence data are absent from published literature; class-level inference from phenmetrazine and amphetamine suggests moderate psychological dependence potential proportional to DAT engagementsupported
Phenmetrazine (parent compound of 3-FPM) attenuates cocaine self-administration in rodents via DA/NE release. Establishes phenmetrazine abuse liability and dopaminergic mechanism. s00213-015-3875-4
history7 · 7 ok
The compound was independently synthesized and analytically characterized in academic literature by McLaughlin and colleagues, published in Drug Testing and Analysis (online 2016, print 2017)supported
First synthesis and analytical characterization of 3-FPM. dta.1945
Their study was prompted by 3-FPM's emergence on the new psychoactive substance (NPS) market; five samples purchased from UK internet vendors all proved to be authentic 3-FPM.supported
Five UK internet vendor samples verified as genuine 3-FPM. Describes 3-FPM as an NPS that appeared on the recreational drug market as a phenmetrazine analog. dta.1945
Phenmetrazine was widely prescribed for weight management but was withdrawn from clinical use in most countries following recognition of its stimulant abuse potential and adverse cardiovascular and psychiatric effectssupported
Systematic review of drugs affecting monoamine neurotransmitters licensed for obesity treatment that were withdrawn due to adverse reactions. Includes phenmetrazine history. s12916-016-0735-y
It remains a Schedule II controlled substance in the United States. Phendimetrazine (Schedule III) serves as a prodrug for phenmetrazine, undergoing hepatic conversion to the active compound.supported
Phendimetrazine (Schedule III) acts as prodrug for phenmetrazine. j.drugalcdep.2012.10.026
3-FPM first appeared on the recreational drug market in 2014, detected in Hungary, Sweden, and the United Kingdomsupported
First patented 2011, appeared on drug market 2014. dta.2577
3-FPM first appeared on the recreational drug market in 2014, detected in Hungary, Sweden, and the United Kingdomsupported
Case series from Swedish Poison Information Centre: 8 analytically confirmed 3-FPM intoxications Nov 2014 - Oct 2015. 15563650.2016.1211288
The Swedish Poisons Information Centre (STRIDA project) logged the first analytically confirmed 3-FPM intoxications in November 2014.supported
8 analytically confirmed 3-FPM intoxications Nov 2014 - Oct 2015. 15563650.2016.1211288
clinical-evidence6 · 6 ok
Cause of death: multiple drug toxicity (accident).supported
Poly-drug death with U-47700, amitriptyline, methamphetamine, diazepam, flubromazolam, delorazepam. bkx060
The only controlled human exposure study is a single-participant pharmacokinetic self-experiment by Grumann et al. 2019supported
PK self-experiment: Cmax 210 ng/mL at tmax 2.5 h after oral ingestion. dta.2577
The STRIDA project (Swedish Poisons Information Centre) reported the largest clinical series: 19 patients with analytically confirmed 3-FPM exposure presenting to Swedish emergency departments between November 2014 and October 2015:partially supported
Case series from Swedish Poison Information Centre: 8 analytically confirmed 3-FPM intoxications Nov 2014 - Oct 2015. 15563650.2016.1211288
The patient required bilateral below-knee amputations and sustained left hand digit necrosissupported
Required bilateral below-knee amputations and prolonged CVVH (26 days). s13730-017-0263-4
The patient was discharged on day 7.supported
Discharged day 7. bcr-2018-224995
Cause of death: positional asphyxia promoted by polydrug intoxication.supported
Cause of death: positional asphyxia from poly-drug intoxication. j.forsciint.2019.109959
pharmacokinetic-detail5 · 5 ok
The single published human pharmacokinetic study (Grumann et al. 2019; n=1 controlled self-experiment, single oral dose) provides the following parameter set:supported
PK self-experiment: Cmax 210 ng/mL at tmax 2.5 h after oral ingestion. T1/2 ~8.8 h, Vd ~400 L (5.3 L/kg). dta.2577
Mardal et al. 2016 established the metabolic profile using rat and human urine samples combined with in vitro CYP isoenzyme incubationssupported
Studies on in vivo metabolism in rat and human, in vitro metabolism in human CYP isoenzymes and microbial biotransformation. j.jpba.2016.06.011
The oxidative ring-opening metabolite 2-amino-1-(3-fluorophenyl)propan-1-ol exhibited the longest detection window across all biological matrices in the Grumann pharmacokinetic study, suggesting it accumulates or clears more slowly than the parent compoundsupported
Ring-opening product (2-amino-1-(3-fluorophenyl)propan-1-ol) showed largest detection window. dta.2577
Specific CYP isoenzyme assignments (CYP2D6, CYP3A4, CYP2B6) are not available from the published abstractsupported
CYP isoenzyme contributions to phase I metabolism characterized. j.jpba.2016.06.011
The intravenous route bypasses first-pass metabolism entirely, producing near-instantaneous peak concentrations — the catastrophic vasoconstrictive injury documented in a published case report is consistent with this pharmacokinetic profile.supported
52-year-old male IV user of 3-FPM developed AKI, four-limb ischaemia with atrial fibrillation, hypotension, livedo reticularis. Highlights severe vasoconstrictive and end-organ effects. s13730-017-0263-4
comparative-pharmacology4 · 4 ok
3-FPM belongs to a series of fluorinated phenmetrazine analogs (2-FPM, 3-FPM, 4-FPM) that share qualitatively similar pharmacology — all function as substrate-type catecholamine releasers with weak serotonergic activitysupported
2-, 3- and 4-FPM inhibit uptake at DAT and NET with IC50 < 2.5 uM (comparable to cocaine), SERT IC50 > 80 uM. FPM isomers act as monoamine releasers via DAT, NET, SERT. j.neuropharm.2017.10.006
The three isomers can be differentiated analytically by NMR, mass spectrometry, and chromatographic methods.supported
Differentiation from 2-FPM and 4-FPM isomers accomplished. dta.1945
The DAT IC₅₀ values for both compounds fall in the low micromolar range, suggesting comparable transporter potencysupported
2-, 3- and 4-FPM inhibit uptake at DAT and NET with IC50 < 2.5 uM (comparable to cocaine). j.neuropharm.2017.10.006
Mayer et al. 2018 explicitly noted that 3-FPM's DAT and NET IC₅₀ values are comparable to cocainesupported
2-, 3- and 4-FPM inhibit uptake at DAT and NET with IC50 < 2.5 uM (comparable to cocaine). j.neuropharm.2017.10.006
neuroscience4 · 3 ok
The parent compound phenmetrazine self-administers in rodents at reinforcing doses, and phenmetrazine-trained rhesus monkeys generalize the discriminative stimulus to amphetamine — confirming that the phenylmorpholine scaffold engages the same mesolimbic circuits as amphetamine-class stimulants.partially supported
Phenmetrazine (parent compound of 3-FPM) attenuates cocaine self-administration in rodents via DA/NE release. Establishes phenmetrazine abuse liability and dopaminergic mechanism. s00213-015-3875-4
The parent compound phenmetrazine self-administers in rodents at reinforcing doses, and phenmetrazine-trained rhesus monkeys generalize the discriminative stimulus to amphetamine — confirming that the phenylmorpholine scaffold engages the same mesolimbic circuits as amphetamine-class stimulants.supported
Drug discrimination studies in rhesus monkeys. Establishes phenmetrazine's pharmacological profile and abuse potential. j.drugalcdep.2012.10.026
Claim in neuroscience — inconclusiveinconclusiveworking →
What is the dose-response curve for reward and reinforcement? No self-administration, conditioned place preference, or intracranial self-stimulation studies have been published for 3-FPM. The parent compound phenmetrazine self-administers in rats, but the fluorine substitution may alter reinforcing efficacy.supported
Phenmetrazine (parent compound of 3-FPM) attenuates cocaine self-administration in rodents via DA/NE release. Establishes phenmetrazine abuse liability and dopaminergic mechanism. s00213-015-3875-4
chemistry2 · 2 ok
All three have been characterized pharmacologically and show qualitatively similar catecholamine-selective releasing activity, though quantitative differences in transporter potency existsupported
2-, 3- and 4-FPM inhibit uptake at DAT and NET with IC50 < 2.5 uM (comparable to cocaine), SERT IC50 > 80 uM. FPM isomers act as monoamine releasers via DAT, NET, SERT. j.neuropharm.2017.10.006
The three isomers can be differentiated analytically by NMR, mass spectrometry, and chromatographic methods.supported
Differentiation from 2-FPM and 4-FPM isomers accomplished. dta.1945
receptor-pharmacology2 · 2 ok
The sole published transporter pharmacology data for 3-FPM derive from Mayer et al. 2018, conducted in HEK293 cells expressing human monoamine transporters and validated in rat brain synaptosomes:supported
FPM isomers act as monoamine releasers via DAT, NET, SERT in HEK293 cells and rat brain synaptosomes. First published pharmacological characterization of 3-FPM mechanism of action. j.neuropharm.2017.10.006
EC₅₀ values for monoamine release — the more pharmacologically relevant metric for a releasing agent — are not reported in published abstracts. The available IC₅₀ values reflect uptake inhibition potency, which does not fully capture releasing efficacysupported
2-, 3- and 4-FPM inhibit uptake at DAT and NET with IC50 < 2.5 uM (comparable to cocaine), SERT IC50 > 80 uM. j.neuropharm.2017.10.006
effects-overview1 · 1 ok
No controlled human studies have assessed subjective effects; all characterization derives from clinical toxicology surveillance and class inference.supported
Case series from Swedish Poison Information Centre: 8 analytically confirmed 3-FPM intoxications Nov 2014 - Oct 2015. Documents adverse events profile for 3-FPM in clinical toxicology setting. 15563650.2016.1211288