generation run 2026-05-07
56 min completedmodel pipeline-v5plan not recordedrun/b5bf389b…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
- sparse_evidence
- structural_inference
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
23 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | OpenAlex | 3-fluoromethamphetamine neurotoxicity dopamine | 10 | 0 | No new unique 3-FMA papers found. |
| 2 | PubMed | fluoromethamphetamine self-administration abuse potential reward | 1 | — | Duplicate; already captured. |
| 3 | PubChem | 3-fluoromethamphetamine | 1 | 1 | Primary chemical identity source; used to verify seed data from brief. |
| 4 | PubMed | fluorinated amphetamine designer drug stimulant pharmacology | 1 | 1 | Relevant fluorinated phenethylamine class pharmacology; mechanism data applicable as contextual analog. |
| 5 | PubMed | 3-fluoromethamphetamine hyperthermia oxidative stress neurotoxicity | 1 | — | Duplicate; already captured. |
| 6 | OpenAlex | 3-fluoromethamphetamine amphetamine designer drug pharmacology | 10 | 1 | Only the Nguyen 2018 paper was directly relevant to 3-FMA. |
| 7 | PubMed | 3-fluoromethamphetamine 3-FMA pharmacology | 2 | 2 | Both papers are primary research directly on 3-FMA pharmacology and toxicology - highest relevance. |
| 8 | ClinicalTrials.gov · absence | 3-fluoromethamphetamine 3-FMA | 0 | — | Absence confirmed - no trials registered. |
| 9 | PubMed | methamphetamine mechanism VMAT2 dopamine amphetamine annual review | 1 | 1 | Essential mechanistic reference for amphetamine class; applicable to 3-FMA. |
| 10 | WebFetch | effects dose tolerance harm reduction | 1 | 2 | Additional dosing route data not in seed DB; tolerance data. |
| 11 | PubMed | amphetamine methamphetamine cardiovascular toxicity hypertension tachycardia | 7 | 2 | Cardiovascular and clinical toxicology data applicable by analog inference. |
| 12 | PubMed | stimulant overamping overdose management ambulatory protocol | 1 | 1 | Directly applicable harm reduction/management guidance for stimulant class overdose. |
| 13 | WebSearch | 3-fluoromethamphetamine EMCDDA new psychoactive substance first appearance market | 10 | 1 | Provides history of 3-FMA market appearance and early regulatory notifications. |
| 14 | WebFetch | dose duration pharmacology effects | 1 | 2 | Confirms seed data doses and durations from community sources. |
| 15 | WebFetch | chemical properties 3-FMA | 1 | 1 | CAS number confirmation. |
| 16 | WebSearch | 3-fluoromethamphetamine fatality Finland England Wales death | 10 | 0 | Confirms fatality link but no published case reports identified. |
| 17 | WebSearch | 3-FMA 3-fluoromethamphetamine legal status scheduling UK EU US controlled substance | 10 | 2 | Legal status data not available via structured APIs; web sources needed. |
| 18 | WebSearch | 3-fluoromethamphetamine CAS 1324717-74-9 SMILES physical properties | 10 | 1 | SMILES not returned by PubChem API call; obtained via web. |
| 19 | PubMed | NPS stimulant wastewater epidemiology Europe prevalence | 5 | 1 | Epidemiological context for NPS stimulant market; 3-FMA belongs to this category. |
| 20 | PubMed · absence | amphetamine analog enantiomer R S stereochemistry pharmacology | 0 | — | Confirms absence of enantiomer data for 3-FMA. |
| 21 | PubMed | stimulant overamping overdose management protocol ambulatory | 1 | 1 | Evidence-based stimulant overdose management applicable to 3-FMA. |
| 22 | Multiple | Cross-reference seed data vs published data | — | — | Systematic verification of all seed data fields. |
| 23 | Multiple PubMed papers | Extract key quantitative values for 3-FMA | — | — | All key pharmacological quantitative data extracted for research output. |
61 claims by section — every cited sentence, checked against its source
safety15 · 10 ok
3-FMA produces dose-dependent mortality in mice at intraperitoneal doses of 40, 60, and 80 mg/kgsupported
3-FMA (40, 60 or 80 mg/kg, i.p.) produced mortality in a dose-dependent manner in mice. j.neuint.2017.11.017
These neurotoxic effects were comparable in magnitude to equimolar methamphetamine.supported
3-FMA significantly produced dopaminergic impairments with behavioral impairments comparable to MA. j.neuint.2017.11.017
Claim in safety — not_supportednot supportedworking →
Chronic exposure carries risk for dilated cardiomyopathy and pulmonary hypertensionpartially supported
Chronic methamphetamine causes hypertension, atherosclerosis, vasospasm, dilated cardiomyopathy. s00059-024-05279-6
Claim in safety — inconclusiveinconclusiveworking →
Hyperthermia is a primary mechanism of acute amphetamine-class toxicity and was directly demonstrated in 3-FMA-treated micesupported
Treatment with 3-FMA (40 mg/kg, i.p.) resulted in significant hyperthermia. j.neuint.2017.11.017
Claim in safety — inconclusiveinconclusiveworking →
Compulsive redosing — the urge to re-dose is reported as a prominent feature and is supported by high-breakpoint progressive-ratio self-administration in rodentssupported
high breakpoints at the dose of 0.3 and 1.0 mg/kg/infusion (i.v.) during 6 hr sessions under progressive ratio schedule of reinforcement in rats. adb.12846
Claim in safety — inconclusiveinconclusiveworking →
Conditioned place preference at 10 and 30 mg/kg i.p. in micesupported
In the CPP procedure, intraperitoneal administration of 3-FMA (10 and 30 mg/kg) produced a significant alteration in place preference in mice. adb.12846
Fixed-ratio intravenous self-administration at 0.1 mg/kg/infusionsupported
3-FMA showed drug-taking behavior at the dose of 0.1 mg/kg/infusion (i.v.) during 2 hr sessions under fixed ratio schedules. adb.12846
High breakpoints at 0.3 and 1.0 mg/kg/infusion on progressive-ratio schedules during 6-hour sessionssupported
high breakpoints at the dose of 0.3 and 1.0 mg/kg/infusion (i.v.) during 6 hr sessions under progressive ratio schedule of reinforcement in rats. adb.12846
Full substitution for methamphetamine in discriminative stimulus paradigmssupported
All fluorinated compounds elicited full substitution for methamphetamine in discriminative stimulus tests (ED50 0.32-0.71 mg/kg). j.jpet.2025.103617
Claim in safety — inconclusiveinconclusiveworking →
CYP2D6 poor metabolizer status — elevated exposure and toxicity risk by analog inference from PMMApartially supported
CYP2D6 is important in PMMA metabolism. CYP2D6 poor metabolizer genotype overrepresented in nonfatal controls. j.forsciint.2016.02.027
comparative-pharmacology8 · 7 ok
The ED₅₀ rank order for locomotor stimulation placed 3-FMA in the mid-range among tested compounds (approximate rank: 2-FMA > methamphetamine ≈ 3-FMA ≈ 3-FA > 4-FMA; ED₅₀ range 0.38–7.38 mg/kg across all compounds).supported
All compounds produced time- and dose-dependent locomotor stimulation (ED50 range 0.38-7.38 mg/kg). 3-FMA showed peak locomotor effects similar to methamphetamine (5905-7758 counts). j.jpet.2025.103617
3-Fluoroethamphetamine (3-FEA) differs from 3-FMA only in the N-alkyl substituent (ethyl vs methyl). 3-FEA is the only close structural analog with published withdrawal data: repeated administration produced hyperactivity and depression-like behavior upon cessation in micesupported
3-FEA (closely related to 3-FMA) withdrawal produced hyperactivity and depression-like behavior after repeated administration and cessation. jnr.25251
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
This confirms that 3-FMA produces interoceptive cues indistinguishable from methamphetamine in trained animals.supported
All fluorinated compounds elicited full substitution for methamphetamine in discriminative stimulus tests (ED50 0.32-0.71 mg/kg). j.jpet.2025.103617
Para-substitution consistently enhances serotonergic properties in the phenethylamine class, predicting that 3-FMA sits closer to methamphetamine on the stimulant–entactogen spectrum while 4-FMA occupies an intermediate position.supported
4-FMA released NE, DA, and 5-HT similarly to MDMA. Para-substituted amphetamines had enhanced serotonergic vs dopaminergic effects vs methamphetamine. j.euroneuro.2014.12.012
3-FMA's discriminative stimulus is indistinguishable from methamphetamine in trained rats, and its reinforcing properties in self-administration paradigms are comparablepartially supported
All fluorinated compounds elicited full substitution for methamphetamine in discriminative stimulus tests. j.jpet.2025.103617
3-FMA's discriminative stimulus is indistinguishable from methamphetamine in trained rats, and its reinforcing properties in self-administration paradigms are comparablepartially supported
high breakpoints at the dose of 0.3 and 1.0 mg/kg/infusion (i.v.) during 6 hr sessions under progressive ratio schedule of reinforcement in rats. adb.12846
The key identified mechanistic difference is the D1-dependent (rather than D2-dependent) neurotoxicity pathwaysupported
SCH23390, a dopamine D1 receptor antagonist, significantly attenuated 3-FMA-induced neurotoxicity. j.neuint.2017.11.017
pharmacology8 · 7 ok
Structure-activity relationship data from fluorinated cathinones and amphetamines confirm that all three transporter families accept fluorinated phenethylamine substrates.supported
3-fluoro-methcathinone and 4-fluoroamphetamine identified as substrates at all three monoamine transporters. jpet.116.236349
Amphetamines also alkalinize vesicular pH, further impairing monoamine sequestration.supported
Mechanisms include exchange diffusion, reverse transport, channel-like transport, weak base properties, phosphorylation, reactive oxygen/nitrogen species. pmid:17209801
Claim in pharmacology — inconclusiveinconclusiveworking →
The selective D1 antagonist SCH23390 significantly attenuated 3-FMA-induced neurotoxicity, while the D2 antagonist sulpiride did not — the inverse of the pattern observed with methamphetamine, where D2 receptors play the larger rolepartially supported
SCH23390, a dopamine D1 receptor antagonist, significantly attenuated 3-FMA-induced neurotoxicity. j.neuint.2017.11.017
The transporter selectivity profile is inferred from positional isomer comparisons: para-substitution consistently enhances serotonergic relative to dopaminergic activity in the phenethylamine class, predicting that the meta-substituted 3-FMA has a more dopamine/norepinephrine-dominant profile than 4-FMAsupported
Para-substituted amphetamines had enhanced serotonergic vs dopaminergic effects vs methamphetamine. j.euroneuro.2014.12.012
Studies on para-methoxymethamphetamine (PMMA) demonstrate that CYP2D6 genetic polymorphisms significantly affect drug exposure and toxicity risk — poor metabolizers accumulate the parent compound, increasing both efficacy and toxicitysupported
Significant influence of CYP2D6 genetics on ring-substituted methamphetamine metabolism. dmd.117.077263
Data from 2-FMA metabolism in human urine confirms that the ring fluorine in fluoromethamphetamines is stable to metabolic defluorination under normal conditions.supported
N-hydroxylation and aliphatic hydroxylation are characteristic metabolic pathways for fluoromethamphetamine isomers. bkac026
CYP2D6 poor metabolizer status should be considered a potential risk factor for elevated exposure and toxicity, by analogy with PMMA.partially supported
CYP2D6 is important in PMMA metabolism. CYP2D6 poor metabolizer genotype overrepresented in nonfatal controls. j.forsciint.2016.02.027
neuroscience6 · 3 ok
Claim in neuroscience — inconclusiveinconclusiveworking →
Claim in neuroscience — inconclusiveinconclusiveworking →
3-FMA activates the mesolimbic dopamine system — the ventral tegmental area (VTA) to nucleus accumbens (NAc) projection — as evidenced by robust conditioned place preference and high-breakpoint progressive-ratio self-administration in rodentssupported
In the CPP procedure, intraperitoneal administration of 3-FMA (10 and 30 mg/kg) produced a significant alteration in place preference in mice... high breakpoints at the dose of 0.3 and 1.0 mg/kg/infusion. adb.12846
The neurotoxic magnitude is comparable to equimolar methamphetamine, but the receptor mechanism differs — 3-FMA neurotoxicity is D1-dependent, while methamphetamine neurotoxicity is D2-dependent.partially supported
3-FMA significantly produced dopaminergic impairments with behavioral impairments comparable to MA. SCH23390, a dopamine D1 receptor antagonist, significantly attenuated 3-FMA-induced neurotoxicity. j.neuint.2017.11.017
The self-administration and reinstatement data from Ryu and colleagues map directly onto the incentive salience framework. 3-FMA produces both liking (conditioned place preference, indicating positive hedonic value) and wanting (progressive-ratio breakpoints and reinstatement, indicating motivational drive that persists beyond extinction)supported
intraperitoneal administration of 3-FMA (10 and 30 mg/kg) produced a significant alteration in place preference... high breakpoints at the dose of 0.3 and 1.0 mg/kg/infusion. adb.12846
Claim in neuroscience — inconclusiveinconclusiveworking →
summary6 · 5 ok
Structurally, it is methamphetamine with a fluorine atom at the meta position of the phenyl ring (molecular weight 167.22 g/mol), yielding a catecholamine-dominant release profile that distinguishes it from the more serotonergic para-substituted isomer 4-FMA.supported
Para-substituted amphetamines had enhanced serotonergic vs dopaminergic effects vs methamphetamine. j.euroneuro.2014.12.012
3-FMA acts through the canonical amphetamine mechanism: entry into presynaptic terminals via monoamine transporters, disruption of vesicular monoamine transporter-2 (VMAT2), and reverse transport of dopamine, norepinephrine, and serotonin into the synapsesupported
Review of amphetamine mechanism at plasmalemmal (DAT) and vesicular (VMAT2) monoamine transporters. Mechanisms include exchange diffusion, reverse transport, channel-like transport, weak base properties. pmid:17209801
Rodent neurotoxicity studies confirm dopaminergic impairment mediated specifically through D1 receptor activation — a mechanistic distinction from methamphetamine, where D2 receptors play a more prominent rolepartially supported
SCH23390, a dopamine D1 receptor antagonist, significantly attenuated 3-FMA-induced neurotoxicity. j.neuint.2017.11.017
Animal studies demonstrate dose-dependent lethality, significant hyperthermia, oxidative stress, and microglial neuroinflammation at supratherapeutic dosessupported
3-FMA (40, 60 or 80 mg/kg, i.p.) produced mortality in a dose-dependent manner in mice. Treatment with 3-FMA (40 mg/kg, i.p.) resulted in significant hyperthermia, oxidative stress and microgliosis. j.neuint.2017.11.017
Rodent self-administration and progressive-ratio data indicate high abuse liability comparable to methamphetaminesupported
high breakpoints at the dose of 0.3 and 1.0 mg/kg/infusion (i.v.) during 6 hr sessions under progressive ratio schedule of reinforcement in rats. adb.12846
Claim in summary — not_supportednot supportedworking →
pharmacokinetic-detail5 · 1 ok
Claim in pharmacokinetic-detail — not_supportednot supportedworking →
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
The ring fluorine remained intact — no defluorinated metabolites were detectedsupported
N-hydroxylation and aliphatic hydroxylation are characteristic metabolic pathways for fluoromethamphetamine isomers. bkac026
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
clinical-evidence4 · 4 ok
One forensic detection study of the structurally related 2-FMA in human urinesupported
2-FMA detected in forensic urine case. bkac026
All pharmacological characterization derives from rodent behavioral and neurochemical studies.supported
Intravenous (i.v.) administration of 3-FMA (0.5 and 1.0 mg/kg) significantly increased locomotor activity in a dose-dependent manner in rats. adb.12846
All pharmacological characterization derives from rodent behavioral and neurochemical studies.supported
3-FMA (40, 60 or 80 mg/kg, i.p.) produced mortality in a dose-dependent manner in mice. j.neuint.2017.11.017
All pharmacological characterization derives from rodent behavioral and neurochemical studies.supported
Investigates 2-FA, 3-FA, 2-FMA, 3-FMA, 4-FMA in mice and rats. j.jpet.2025.103617
receptor-pharmacology4 · 3 ok
The para-substituted isomer 4-FMA releases norepinephrine, dopamine, and serotonin with a selectivity profile comparable to MDMA, demonstrating enhanced serotonergic activity relative to unsubstituted methamphetamine. 4-FMA also shows TAAR1 (trace amine-associated receptor 1) bindingsupported
4-FMA released NE, DA, and 5-HT similarly to MDMA. Para-substituted amphetamines had enhanced serotonergic vs dopaminergic effects vs methamphetamine. TAAR1 binding also assessed. j.euroneuro.2014.12.012
Structure-activity data from broader fluorinated phenethylamine series confirm that fluorinated analogs act as substrates (not blockers) at DAT, NET, and SERT — maintaining the releasing mechanism rather than converting to reuptake inhibition.supported
3-fluoro-methcathinone and 4-fluoroamphetamine identified as substrates at all three monoamine transporters. jpet.116.236349
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Nguyen and colleagues demonstrated that D1 receptor antagonism (SCH23390) significantly attenuated 3-FMA-induced striatal neurotoxicity, while D2 receptor antagonism (sulpiride) had no protective effectpartially supported
SCH23390, a dopamine D1 receptor antagonist, significantly attenuated 3-FMA-induced neurotoxicity. j.neuint.2017.11.017
history3 · 0 ok
chemistry2 · 2 ok
Meta-positioned fluorine is predicted to produce a more dopamine/norepinephrine-dominant pharmacological profile compared to para-substitution, which consistently enhances serotonergic activity in the phenethylamine class.supported
Para-substituted amphetamines had enhanced serotonergic vs dopaminergic effects vs methamphetamine. j.euroneuro.2014.12.012
The ring-positioned fluorine is metabolically stable to defluorination under normal physiological conditions, based on data from the structurally analogous 2-FMA.supported
N-hydroxylation and aliphatic hydroxylation are characteristic metabolic pathways for fluoromethamphetamine isomers. bkac026