generation run 2026-04-21
58 min completedmodel pipeline-v5plan not recordedrun/380f884a…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
- sparse_evidence
- no_withdrawal_data
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
20 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | ClinicalTrials.gov · absence | 5-MAPB benzofuran | 0 | 0 | No results - confirms no registered clinical trials |
| 2 | PubMed · absence | 5-APB benzofuran receptor binding affinity monoamine releasing agent serotonin dopamine | 0 | 0 | Expanded search returned no new results |
| 3 | OpenAlex | 5-MAPB 5-APB benzofuran pharmacology binding affinity transporter | 8 | 2 | Rickli 2015 is the landmark pharmacology paper. Shimshoni 2017 directly characterizes 5-MAPB binding profile |
| 4 | PubChem | 5-MAPB | 1 | 1 | Primary chemical identity verification |
| 5 | PubMed | Shimshoni 2017 benzofuran MDMA analogues neurochemical binding | 1 | 1 | Directly characterizes 5-MAPB binding profile — essential for pharmacology section |
| 6 | PubMed | 5-APB 6-APB benzofuran monoamine transporter release dopamine serotonin norepinephrine | 2 | 2 | Core pharmacology papers — Rickli 2015 has 115 citations and directly characterizes benzofurans including 5-MAPB at monoamine transporters and 5-HT receptors |
| 7 | PubMed | 5-MAPB benzofuran entactogen pharmacology | 2 | 2 | Both directly relevant to 5-MAPB pharmacology and metabolism |
| 8 | OpenAlex | 5-MAPB methylaminopropyl benzofuran psychoactive | 8 | 4 | Case reports, pharmacology, forensic toxicology directly relevant to 5-MAPB |
| 9 | PubMed | MDMA serotonin syndrome interaction MAO inhibitor fatal | 2 | 2 | Establish serotonin syndrome risk for serotonin releasing agents like 5-MAPB combined with MAOIs |
| 10 | PubMed | 5-EAPB MDAI benzofuran death forensic blood concentration | 1 | 1 | Postmortem blood concentration data for 5-MAPB; fatality context |
| 11 | OpenAlex | benzofuran NPS scheduling legal control UK temporary class drug order | 8 | 2 | Major NPS review covering benzofurans; legal status context |
| 12 | UK legislation.gov.uk (WebFetch) | 5-MAPB 5-APB 6-APB UK scheduling Class B MODA 2014 | 1 | 2 | Confirms UK legal status for 5-MAPB |
| 13 | PubMed | benzofuran cross-reactivity immunoassay amphetamine ecstasy | 1 | 1 | Relevant to drug testing and harm reduction section |
| 14 | PubMed | 5-MAPB alpha-methyltryptamine AMT fatal co-intoxication | 1 | 1 | Only published fatal case report specifically naming 5-MAPB as a primary substance |
| 15 | PubMed Central (via WebFetch) | 5-MAPB 5-APB 6-APB EC50 values monoamine transporter synaptosome | 1 | 1 | Core quantitative pharmacology data for 5-MAPB specifically |
| 16 | PubMed | MDMA bioisosteric analogs benzofuran pharmacological profile | 1 | 1 | Comparative pharmacology of MDMA scaffold analogs; supports 5-HT receptor activity data for benzofurans |
| 17 | PubMed | MDAI 2-MAPB postmortem redistribution forensic | 1 | 1 | Relevant to interpreting postmortem 5-MAPB blood concentrations in fatal cases |
| 18 | UK legislation.gov.uk / ACMD | benzofuran 5-MAPB scheduling UK Class B MODA TCDO 2013 2014 | 1 | 2 | Primary UK legal status documentation |
| 19 | DEA / eCFR (WebFetch - failed) · absence | 5-MAPB DEA schedule I controlled substance benzofuran analog | 0 | 0 | Unable to confirm - flagged as gap requiring manual verification |
| 20 | PubMed | alpha-methyltryptamine AMT metabolite postmortem blood | 1 | 1 | Context for interpreting AMT role in the fatal co-intoxication case involving 5-MAPB |
76 claims by section — every cited sentence, checked against its source
safety20 · 15 ok
The single published fatality involving 5-MAPB as a primary substance of concern was a polydrug co-intoxication: postmortem peripheral blood contained 5-MAPB at 101 ng/mL alongside AMT (4,690 ng/mL), benzodiazepines, ephedrine, and norephedrinesupported
Fatal co-intoxication: AMT (4690 ng/mL) and 5-MAPB (101 ng/mL) in postmortem peripheral blood, combined with benzodiazepines, ephedrine, and norephedrine. s00414-024-03236-w
A second death attributed to 5-EAPB (6.45 mg/L) and MDAI (2.09 mg/L) detected 5-MAPB at 0.089 mg/L, likely as a co-ingestant or metabolic product.supported
Fatal case: 5-EAPB (6.45 mg/L) and MDAI (2.09 mg/L) as primary substances. 5-MAPB also detected in blood (0.089 mg/L) and urine (1.00 mg/L). j.forsciint.2019.03.023
Non-fatal clinical cases showed plasma concentrations of 5–124 μg/L without reported organ damage, though systematic clinical follow-up data are absent.supported
Plasma concentrations in 6 clinical cases: 5-124 ug/L for 5-MAPB, 1-38 ug/L for 5-APB metabolite. s00216-014-8360-0
Acute cardiovascular toxicity arises from the sympathomimetic mechanism: combined norepinephrine and dopamine release produces tachycardia, hypertension, and peripheral vasoconstrictionsupported
Stimulants (amphetamines, cathinones) primarily interact with monoamine transporters producing sympathomimetic adverse effects. Benzofurans covered as MDMA analogs. s00204-020-02693-7
The noradrenergic α₂ receptor binding documented for 5-MAPB may amplify cardiovascular stress beyond that predicted by transporter release alone.supported
5-MAPB characterized for high binding affinities at 5-HT2a,b,c and NEa2 receptors. s00210-016-1297-4
Chronic cardiac risk: 5-HT₂B receptor agonism raises theoretical concern for cardiac valvulopathy (pulmonary and tricuspid valve fibrosis) with repeated exposuresupported
Benzofurans induce 5-HT2B receptor activation associated with heart valve fibrosis. bph.13128
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Dependence: 5-MAPB fully substitutes for MDMA in drug discrimination at more potent doses, confirming abuse potentialsupported
All compounds more potent than MDMA. All three fully substituted in MDMA-trained rats. Benzofuran compounds may have abuse liability as substitutes for MDMA. j.dadr.2023.100182
Claim in safety — inconclusiveinconclusiveworking →
The combination with MAO inhibitors is the highest-risk interaction: four deaths from MDMA combined with the reversible MAOI moclobemide are documented, and the identical mechanism applies to 5-MAPBsupported
Four fatal cases of serotonin toxicity from MDMA+moclobemide combination. Symptoms: hyperthermia, hyperkalemia, profuse sweating, twitching, shaking. j.forsciint.2011.04.008
The combination with MAO inhibitors is the highest-risk interaction: four deaths from MDMA combined with the reversible MAOI moclobemide are documented, and the identical mechanism applies to 5-MAPBsupported
Four deaths following ingestion of moclobemide and MDMA. Probable cause of death serotonin syndrome from drug interaction. pmid:12603236
The preliminary finding that 5-MAPB itself inhibits MAO-A would compound this risk — co-administration with an external MAOI could produce catastrophic serotonin accumulation.supported
potent MAO-A inhibition. s00210-016-1297-4
The fatal polydrug case involving 5-MAPB included ephedrine and norephedrine alongside AMT, illustrating the combined sympathomimetic burden in NPS polysubstance use.supported
Fatal co-intoxication: AMT (4690 ng/mL) and 5-MAPB (101 ng/mL) in postmortem peripheral blood, combined with benzodiazepines, ephedrine, and norephedrine. s00414-024-03236-w
CYP2B6 inducers (rifampicin, carbamazepine) could reduce plasma levels and potentially shift the metabolite ratio.supported
CYP2B6 responsible for main CYP-dependent clearance. s00216-014-8360-0
Concurrent MAO inhibitor use — irreversible (phenelzine, tranylcypromine) or reversible (moclobemide). Fatal serotonin syndrome risk is documented for MDMA + MAOI combinations and applies identically to 5-MAPB.supported
Four fatal cases of serotonin toxicity from MDMA+moclobemide combination. Confirms fatal serotonin syndrome risk with MAOI+serotonin releaser combinations. j.forsciint.2011.04.008
Concurrent MAO inhibitor use — irreversible (phenelzine, tranylcypromine) or reversible (moclobemide). Fatal serotonin syndrome risk is documented for MDMA + MAOI combinations and applies identically to 5-MAPB.supported
Four deaths following ingestion of moclobemide and MDMA. Probable cause of death serotonin syndrome from drug interaction. pmid:12603236
CYP2B6/CYP2D6 poor metabolizer status — elevated plasma exposure and potentially altered metabolite ratios.supported
CYP enzymes involved: CYP1A2, CYP2B6, CYP2C19, CYP2D6; CYP2B6 responsible for main CYP-dependent clearance. s00216-014-8360-0
summary13 · 6 ok
1-(1-Benzofuran-5-yl)-N-methylpropan-2-amine (5-MAPB) is a substituted benzofuran of the entactogen-stimulant class, structurally analogous to MDMA as the N-methyl derivative of 5-APB — paralleling the methamphetamine-to-amphetamine relationshipsupported
Main metabolites of 5-MAPB: 5-APB (N-demethyl) and 3-carboxymethyl-4-hydroxy methamphetamine. s00216-014-8360-0
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Additional agonist activity at 5-HT₂B and 5-HT₂C receptors and preliminary evidence of MAO-A inhibition have been documented.supported
5-MAPB characterized for high binding affinities at 5-HT2a,b,c and NEa2 receptors... agonist activity at 5-HT2c; potent MAO-A inhibition. s00210-016-1297-4
In MDMA-trained rats, 5-MAPB fully substitutes at doses more potent than MDMA itself, predicting an entactogenic experiential profile encompassing euphoria, emotional closeness, stimulation, and mild perceptual enhancementsupported
All compounds more potent than MDMA. All three fully substituted in MDMA-trained rats. Benzofuran compounds may have abuse liability as substitutes for MDMA. j.dadr.2023.100182
Claim in summary — not_supportednot supportedworking →
No LD₅₀ data exist for any species, and no human fatality has been attributed solely to 5-MAPB — the single published fatal case involved polydrug co-intoxicationsupported
Fatal co-intoxication: AMT (4690 ng/mL) and 5-MAPB (101 ng/mL) in postmortem peripheral blood, combined with benzodiazepines, ephedrine, and norephedrine. s00414-024-03236-w
The principal acute risks are cardiovascular strain from sympathomimetic activity and serotonin syndrome in polydrug combinations, particularly with MAO inhibitors where the risk is lethalsupported
Four fatal cases of serotonin toxicity from MDMA+moclobemide combination. Symptoms: hyperthermia, hyperkalemia, profuse sweating, twitching, shaking. j.forsciint.2011.04.008
Agonism at 5-HT₂B receptors raises theoretical concern for cardiac valvulopathy with chronic exposure, though no cases have been published for this compoundsupported
Benzofurans induce 5-HT2B receptor activation associated with heart valve fibrosis. bph.13128
pharmacology9 · 8 ok
This mechanism is qualitatively identical to MDMA: the compound enters the transporter as a substrate and reverses its direction, causing non-exocytotic release of stored neurotransmitter.supported
Benzofurans acted as indirect monoamine agonists that interact with transporters similarly to MDMA. bph.13128
Claim in pharmacology — inconclusiveinconclusiveworking →
Beyond transporter-mediated release, 5-MAPB exhibits direct agonist activity at serotonin receptors, with high binding affinity for 5-HT₂A, 5-HT₂B, and 5-HT₂C subtypes and significant functional agonism at 5-HT₂Csupported
5-MAPB characterized for high binding affinities at 5-HT2a,b,c and NEa2 receptors... agonist activity at 5-HT2c. s00210-016-1297-4
The 5-HT₂B agonism is of particular clinical concern: chronic activation of this receptor subtype is associated with cardiac valvulopathy (fibrotic thickening of heart valves), a mechanism established through the fenfluramine precedentsupported
Benzofurans induce 5-HT2B receptor activation associated with heart valve fibrosis. bph.13128
Significant norepinephrine α₂ receptor binding has also been documented.supported
5-MAPB characterized for high binding affinities at 5-HT2a,b,c and NEa2 receptors. s00210-016-1297-4
A preliminary finding of potent MAO-A inhibition by 5-MAPB carries substantial clinical significance if confirmed: dual monoamine release combined with monoamine oxidase inhibition would create a self-potentiating serotonergic effect, elevating baseline serotonin toxicity risk beyond that of MDMA alone.supported
potent MAO-A inhibition. All MDMA analogues displayed higher monoamine receptor/transporter binding affinities than MDMA. s00210-016-1297-4
In rat models and confirmed in six human clinical cases, the primary metabolic pathway proceeds via N-demethylation to the active metabolite 5-APB, followed by ring hydroxylation and oxidative ring-opening to 3-carboxymethyl-4-hydroxymethamphetaminesupported
Main metabolites of 5-MAPB: 5-APB (N-demethyl) and 3-carboxymethyl-4-hydroxy methamphetamine... Plasma concentrations in 6 clinical cases. s00216-014-8360-0
The N-demethylation step is catalyzed by CYP1A2, CYP2B6, CYP2C19, and CYP2D6, with CYP2B6 responsible for the majority of total CYP-dependent clearance.supported
CYP enzymes involved: CYP1A2, CYP2B6, CYP2C19, CYP2D6; CYP2B6 responsible for main CYP-dependent clearance. s00216-014-8360-0
In six clinical cases (doses unknown), plasma concentrations ranged from 5–124 μg/L for 5-MAPB and 1–38 μg/L for the 5-APB metabolitesupported
Plasma concentrations in 6 clinical cases: 5-124 ug/L for 5-MAPB, 1-38 ug/L for 5-APB metabolite. s00216-014-8360-0
clinical-evidence7 · 6 ok
Six clinical cases (non-fatal, doses unknown) yielded 5-MAPB plasma concentrations of 5–124 μg/L and 5-APB metabolite concentrations of 1–38 μg/Lsupported
Plasma concentrations in 6 clinical cases: 5-124 ug/L for 5-MAPB, 1-38 ug/L for 5-APB metabolite. s00216-014-8360-0
A fatal co-intoxication case reported 5-MAPB at 101 ng/mL in postmortem peripheral blood, with concurrent AMT (4,690 ng/mL), benzodiazepines, ephedrine, and norephedrinesupported
Fatal co-intoxication: AMT (4690 ng/mL) and 5-MAPB (101 ng/mL) in postmortem peripheral blood, combined with benzodiazepines, ephedrine, and norephedrine. s00414-024-03236-w
In a separate fatality primarily attributed to 5-EAPB (6.45 mg/L) and MDAI (2.09 mg/L), 5-MAPB was detected at 0.089 mg/L alongside 5-APB at 0.546 mg/L. 5-MAPB was either co-ingested or a metabolic product of 5-EAPB metabolism.supported
Fatal case: 5-EAPB (6.45 mg/L) and MDAI (2.09 mg/L) as primary substances. 5-MAPB also detected in blood (0.089 mg/L) and urine (1.00 mg/L), and 5-APB in blood (0.546 mg/L). j.forsciint.2019.03.023
Hair analysis confirmed chronic repeated benzofuran use over the preceding monthssupported
Emergency department case positive for 5-MAPB, 5-APB, 5-EAPB, ethylphenidate in urine, serum, and hair segments evidencing repeated use. s00414-017-1648-9
Claim in clinical-evidence — inconclusiveinconclusiveworking →
Benzofurans including 5-MAPB cross-react with commercial immunoassay screening tests for amphetamines and ecstasy in urinesupported
Cross-reactivity investigation of six benzofurans including 5-MAPB with commercial immunoassay screening tests for amphetamines and ecstasy in urine samples. bio-2017-0191
Confirmatory analysis by GC-MS or LC-MS/MS is required for specific identification and quantification.supported
studies on the metabolism and toxicological analysis of 5-APB and 5-MAPB in urine and plasma using GC-MS and LC-(HR)-MSn techniques s00216-014-8360-0
neuroscience7 · 6 ok
What is the contribution of MAO-A inhibition to the overall effect? If the preliminary MAO-A inhibition finding is confirmed, the serotonergic pharmacodynamics of 5-MAPB would differ qualitatively from MDMA — potentially increasing both therapeutic potential and toxicity risk.supported
potent MAO-A inhibition. All MDMA analogues displayed higher monoamine receptor/transporter binding affinities than MDMA. s00210-016-1297-4
The following neural mechanisms are inferred from the well-characterized pharmacology of MDMA and the empatho-entactogen class, applied to 5-MAPB based on its confirmed MDMA-like transporter activity and discriminative stimulus properties.supported
Benzofurans acted as indirect monoamine agonists that interact with transporters similarly to MDMA. Benzofurans also interacted with 5-HT receptors resulting in MDMA-like entactogenic properties. bph.13128
The following neural mechanisms are inferred from the well-characterized pharmacology of MDMA and the empatho-entactogen class, applied to 5-MAPB based on its confirmed MDMA-like transporter activity and discriminative stimulus properties.supported
All three fully substituted in MDMA-trained rats. j.dadr.2023.100182
Direct 5-HT₂C agonism adds a receptor-mediated serotonergic component beyond transporter-mediated release. 5-HT₂C activation in cortical and limbic circuits is associated with mood modulation, anxiety regulation, and appetite suppressionsupported
agonist activity at 5-HT2c. s00210-016-1297-4
Norepinephrine release (NET EC₅₀ 24 nM — the most potent transporter target) combined with α₂ receptor binding drives sympathetic nervous system activation: elevated heart rate, blood pressure, pupil dilation, and peripheral vasoconstrictionsupported
5-MAPB characterized for high binding affinities at 5-HT2a,b,c and NEa2 receptors; significant 5-HT, DA, NE uptake inhibition. s00210-016-1297-4
Claim in neuroscience — inconclusiveinconclusiveworking →
What are the enantioselective neural effects? Given the probable stereoselective transporter activity (inferred from related 5-MABB data), the R- and S-enantiomers may produce qualitatively different neural activation patterns.supported
S isomers of 5-MABB and 6-MABB are efficacious releasing agents at SERT, NET, and DAT. R isomers are SERT/partial NET releasers lacking DAT releasing activity. jpet.123.001837
comparative-pharmacology6 · 2 ok
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Despite this pharmacological difference, 5-MAPB fully substitutes for MDMA in drug discrimination at more potent doses, confirming qualitatively similar subjective propertiessupported
All compounds more potent than MDMA. All three fully substituted in MDMA-trained rats. j.dadr.2023.100182
A key pharmacological distinction is 5-MAPB's preliminary MAO-A inhibitory activity, which has not been reported for MDMAsupported
potent MAO-A inhibition. All MDMA analogues displayed higher monoamine receptor/transporter binding affinities than MDMA. s00210-016-1297-4
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
history4 · 4 ok
The first published analytical characterization appeared in 2015, when Welter et al. described rat metabolism studies and human clinical plasma concentrations generated in response to 5-MAPB's emergence as a novel psychoactive substancesupported
Main metabolites of 5-MAPB: 5-APB (N-demethyl)... Plasma concentrations in 6 clinical cases. s00216-014-8360-0
That same year, Rickli et al. provided the first comprehensive in vitro pharmacological characterization of the benzofuran class, establishing monoamine transporter interaction profiles and serotonin receptor activitysupported
Benzofurans acted as indirect monoamine agonists that interact with transporters similarly to MDMA. Benzofurans also interacted with 5-HT receptors resulting in MDMA-like entactogenic properties. bph.13128
Academic interest has continued through behavioral pharmacology studies confirming MDMA-like discriminative stimulus properties and abuse potential in animal models, and through medicinal chemistry programs exploring novel benzofuran derivatives using 5-MAPB as a reference entactogensupported
All three fully substituted in MDMA-trained rats. Benzofuran compounds may have abuse liability as substitutes for MDMA. j.dadr.2023.100182
Academic interest has continued through behavioral pharmacology studies confirming MDMA-like discriminative stimulus properties and abuse potential in animal models, and through medicinal chemistry programs exploring novel benzofuran derivatives using 5-MAPB as a reference entactogensupported
5-MAPB used as reference compound... Aminoalkyl benzofuran scaffold viable for MDMA-like compound development. jpet.123.001837
receptor-pharmacology4 · 3 ok
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
5-MAPB demonstrates high binding affinity for 5-HT₂A, 5-HT₂B, and 5-HT₂C receptors, exceeding MDMA's affinity at all three subtypessupported
5-MAPB characterized for high binding affinities at 5-HT2a,b,c and NEa2 receptors... All MDMA analogues displayed higher monoamine receptor/transporter binding affinities than MDMA. s00210-016-1297-4
5-HT₂B agonism was documented for the benzofuran class as a wholesupported
Benzofurans induce 5-HT2B receptor activation associated with heart valve fibrosis. bph.13128
Preliminary data indicate potent MAO-A inhibition by 5-MAPBsupported
potent MAO-A inhibition. s00210-016-1297-4
pharmacokinetic-detail3 · 2 ok
Observed plasma concentrations in clinical cases (5–124 μg/L) confirm oral absorption, but quantitative absorption parameters remain uncharacterized.supported
Plasma concentrations in 6 clinical cases: 5-124 ug/L for 5-MAPB. s00216-014-8360-0
The metabolic pathway has been characterized in rat hepatocyte incubations and confirmed in human clinical specimens:supported
Main metabolites of 5-MAPB: 5-APB (N-demethyl) and 3-carboxymethyl-4-hydroxy methamphetamine... Plasma concentrations in 6 clinical cases. s00216-014-8360-0
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
chemistry2 · 2 ok
The bioisosteric substitution — replacing the 3,4-methylenedioxy bridge with a furan ring fused at the 4,5-position of the phenyl ring — preserves monoamine releasing pharmacology while altering receptor selectivity and metabolic stability.supported
MDMA bioisosteres investigated as potential therapeutic alternatives. Benzofuran scaffold discussed as MDMA analog. 5-HT2A/2B/2C receptor agonist activity assessed for MDMA analogs. jnc.16149
Within the benzofuran series, 5-MAPB is the N-methyl derivative of 5-APB, paralleling the amphetamine-to-methamphetamine structural relationshipsupported
Main metabolites of 5-MAPB: 5-APB (N-demethyl)... s00216-014-8360-0
legal-status1 · 1 ok
In jurisdictions with analog legislation (notably the United States), 5-MAPB's structural similarity to MDMA (Schedule I) and MDA (Schedule I) — confirmed by identical monoamine releasing mechanism and full MDMA substitution in drug discrimination — provides the basis for prosecution under the Federal Analogue Actsupported
Benzofurans acted as indirect monoamine agonists that interact with transporters similarly to MDMA. bph.13128