generation run 2026-04-28
76 min completedmodel pipeline-v5plan not recordedrun/ac4bed38…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
- sparse_evidence
- class_context
Reproduce
- inputs
- 25 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
22 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | PubMed | 5-APB 1-(benzofuran-5-yl)propan-2-amine toxicology | 1 | 1 | Duplicate of prior search; Shimshoni 2017 already selected |
| 2 | PubMed | PMID 25765500 | 1 | 1 | Full retrieval to verify binding data details |
| 3 | PubChem | 5-APB | 1 | 1 | Primary chemical identity verification; confirms brief systematic name and provides missing InChIKey, formula, weight |
| 4 | ClinicalTrials.gov · absence | 5-APB benzofuranylpropylamine | 0 | 0 | No relevant trials; confirms absence of registered clinical research |
| 5 | PubMed | 5-APB 6-APB benzofuran monoamine transporter binding affinity serotonin dopamine | 2 | 2 | Core pharmacology papers with receptor binding/transporter data |
| 6 | PubMed | 5-APB 6-APB benzofuran metabolism metabolite CYP detection urine | 1 | 1 | Key metabolism paper for benzofuran isomers including 5-APB |
| 7 | PubMed | Baumann benzofuran aminopropyl rat microdialysis serotonin | 1 | 1 | Duplicate; Baumann 2020 confirmed |
| 8 | OpenAlex | 5-APB 6-APB benzofuran amphetamine pharmacology entactogen | 10 | 3 | High-citation reviews covering benzofuran pharmacology context; Rickli 2015 confirmed as landmark benzofuran pharmacology paper |
| 9 | PubMed | benzofuran aminopropyl new psychoactive substance case report overdose death | 1 | 1 | Key fatal case report directly involving 5-APB |
| 10 | PubMed | 5-APB benzofuranylpropylamine pharmacology | 15 | 15 | All directly relevant to 5-APB pharmacology, toxicology, or case reports |
| 11 | WebSearch | 5-APB legal status UK Misuse Drugs Act scheduling controlled 2012 2014 | 10 | 2 | UK government primary source for scheduling dates and legal controls |
| 12 | UK Harm Reduction Website | — | 1 | 2 | Secondary harm reduction source confirming legal status and clinical effects |
| 13 | WebSearch | 5-APB benzofury history first appearance research chemical market 2010 2011 | 10 | 1 | Historical context; primary synthesis attribution and market appearance dates |
| 14 | PubChem REST API | — | 1 | 4 | Critical chemical identity data including SMILES not returned by the MCP PubChem tool |
| 15 | WebSearch | 5-APB legal status United States DEA analog act schedule scheduling Australia Canada | 10 | 1 | International legal status from multiple jurisdictions |
| 16 | ClinicalTrials.gov · absence | 5-APB benzofuranylpropylamine | 0 | 0 | Confirms no active clinical research on 5-APB |
| 17 | UK Government website | — | 1 | 1 | Primary UK government source confirming temporary scheduling details |
| 18 | PubChem REST API (JSON) | — | 1 | 1 | Critical for chemical identity section - SMILES not returned by MCP tool |
| 19 | OpenAlex | benzofuran 5-APB receptor binding SERT DAT NET release | 8 | 2 | Confirmed Rickli 2015 key conclusions from OpenAlex abstract; added Rudin 2021 as comparative pharmacology |
| 20 | Multiple | Cross-referencing seed data against published sources | 29 | 0 | Final cross-reference to confirm data consistency and flag gaps |
| 21 | PubMed · absence | tramadol serotonergic drug interaction serotonin syndrome fatal; 5-APB hyperthermia clinical; Nichols MDMA alternative | 0 | 0 | Negative results documented; tramadol interaction and Nichols synthesis will be flagged as unverified in output |
| 22 | UK Harm Reduction Website | — | 1 | 3 | Secondary harm reduction source for UK context and clinical effects |
86 claims by section — every cited sentence, checked against its source
safety26 · 25 ok
Murine data for the closely related 5-MAPB demonstrate a narrower safety margin than MDMA: administration of 5-MAPB at 1.6 × 10⁻⁴ mol/kg caused death in two-thirds of mice, while the same dose of MDMA caused no deaths. 5-APB — as the demethylation metabolite of 5-MAPB — was implicated in the lethal mechanism.partially supported
5-MAPB more potent than MDMA; caused hyperthermia (+3.41°C vs +1.85°C for MDMA). 5-APB noted as metabolic demethylation product of 5-MAPB; may contribute to acute 5-HT toxicity and lethal intoxication in mice. jts.41.329
0.86 mg/L (860 ng/mL) — 25-year-old male; 5-APB as primary agent, with low-level ethanol (0.6 g/L) and trace THC.supported
Fatal case: 25-year-old male... Post-mortem femoral blood: 5-APB 0.86 mg/L, ethanol 0.6 g/L, THC 0.0024 mg/L. Cause of death attributed to 5-APB. j.forsciint.2018.08.044
5.6 µg/mL (5,600 ng/mL) — mixed intoxication with approximately 400 mg 5-APB, approximately 500 mg 3-MMC, and ethanol 1.4 g/L; acute cardiovascular collapse approximately four hours post-ingestion.supported
Patient took ~500 mg 3-MMC and ~400 mg 5-APB with ~80g ethanol. Clinical: agitation, seizures, hypertension, tachycardia, hyperthermia, bradycardia. Died ~4h after use. Post-mortem blood: 5-APB 5.6 µg/mL. j.forsciint.2014.10.016
A third fatality primarily attributed to 5-EAPB and MDAI detected 5-APB at 0.546 mg/L in blood, likely as a metabolic product.supported
Fatal case involving 5-EAPB and MDAI. Also detected: 5-APB in blood (5-APB: 0.546 mg/L) and urine. Demonstrates co-occurrence of 5-APB as metabolite/adulterant. j.forsciint.2019.03.023
5-APB is more hepatotoxic than its positional isomer 6-APB across all tested in vitro cell models:supported
In vitro hepatotoxicity: 5-APB EC50 HepaRG 2.62 mM, HepG2 3.79 mM, primary rat hepatocytes 964 µM. ... 5-APB more hepatotoxic than 6-APB isomer. s00204-019-02638-9
Claim in safety — inconclusiveinconclusiveworking →
Both 5-MAPB and 5-APB produce hepatocyte cytotoxicity via mitochondrial permeability transition, with both compounds more toxic than MDMA to isolated rat hepatocytes.supported
Mitochondrial failure (permeability transition, membrane potential, ATP depletion) drives cytotoxicity. Both benzofurans more toxic than MDMA. jat.3351
CYP3A4-mediated metabolic activation contributes to this hepatotoxicity — co-inhibition of CYP3A4 attenuated the toxic effect, confirming that Phase I metabolism generates reactive intermediates.supported
CYP3A4 involved in toxic metabolism. s00204-019-02638-9
5-APB is a potent full agonist at 5-HT₂B receptors at sub-100 nM concentrations. 5-HT₂B agonism is the established mechanism for drug-induced cardiac valvulopathy — sustained receptor activation causes fibroblast proliferation in valvular tissue, leading to thickening and regurgitationsupported
5-APB and 6-APB showed <100 nM affinity for 5-HT2B and alpha2C receptors. Both confirmed as potent full agonists at 5-HT2B receptors. j.ejphar.2012.12.006
5-APB is a potent full agonist at 5-HT₂B receptors at sub-100 nM concentrations. 5-HT₂B agonism is the established mechanism for drug-induced cardiac valvulopathy — sustained receptor activation causes fibroblast proliferation in valvular tissue, leading to thickening and regurgitationsupported
5-HT2B receptor activation identified as cardiac risk. bph.13128
5-APB is a potent full agonist at 5-HT₂B receptors at sub-100 nM concentrations. 5-HT₂B agonism is the established mechanism for drug-induced cardiac valvulopathy — sustained receptor activation causes fibroblast proliferation in valvular tissue, leading to thickening and regurgitationsupported
Systematic review of 5-HT2B receptor agonism and cardiac valvulopathy. Both LSD and MDMA have high affinity for 5-HT2B and promote downstream fibrotic signaling. a-2794-6487
5-APB is a potent full agonist at 5-HT₂B receptors at sub-100 nM concentrations. 5-HT₂B agonism is the established mechanism for drug-induced cardiac valvulopathy — sustained receptor activation causes fibroblast proliferation in valvular tissue, leading to thickening and regurgitationsupported
5-HT2B receptor activation identified as cardiac risk. bph.13128
Acute psychological adverse effects documented in case reports and harm reduction sources include agitation, disorientation, anxiety, panic, confusion, paranoia, and hallucinations at toxic dosessupported
Symptoms: ... agitation, disorientation, hallucinations, convulsions, reduced consciousness. j.annemergmed.2016.03.042
Dependence liability is assessed as moderate, comparable to MDMA, based on two lines of evidence: 5-APB fully substitutes for MDMA in rat drug discrimination paradigms, and MDMA analogs including benzofurans have addictive properties linked to dopamine signaling in the nucleus accumbenssupported
5-APB fully substituted for MDMA discriminative stimulus, but only partially or not at all for methamphetamine, cocaine, and DOM. Indicates MDMA-like abuse pattern expected. j.drugalcdep.2017.07.041
Dependence liability is assessed as moderate, comparable to MDMA, based on two lines of evidence: 5-APB fully substitutes for MDMA in rat drug discrimination paradigms, and MDMA analogs including benzofurans have addictive properties linked to dopamine signaling in the nucleus accumbenssupported
Review of rewarding and addictive properties of NPS including MDMA analogs (benzofurans). Dopamine signaling in nucleus accumbens central to reinforcing properties. fnins.2016.00153
The combination of serotonin release (SERT reversal), MAO-A inhibition, and direct 5-HT₂ agonism makes 5-APB one of the more pharmacologically complex entactogens with respect to serotonin syndrome risksupported
5-APB showed significant agonist activity at 5-HT2a,b,c receptors and significant 5-HT, DA, NE uptake inhibition. MDMA analogues including 5-APB emerged as potent MAO-A inhibitors. s00210-016-1297-4
The acute toxidrome documented in case reports — hyperthermia, clonus, hyperreflexia, agitation, confusion — overlaps substantially with Hunter's criteria for serotonin syndrome.supported
Symptoms: mild hyperthermia, mydriasis, tremor, hyperreflexia, clonus, agitation, disorientation, hallucinations, convulsions, reduced consciousness. j.annemergmed.2016.03.042
MAOIs are absolutely contraindicated: 5-APB is itself a MAO-A inhibitor, and exogenous MAOI co-administration would produce compounded monoamine accumulation.supported
MDMA analogues including 5-APB emerged as potent MAO-A inhibitors. s00210-016-1297-4
Alcohol: Co-present in both documented fatal cases (ethanol 0.6–1.4 g/L)supported
Post-mortem femoral blood: 5-APB 0.86 mg/L, ethanol 0.6 g/L, THC 0.0024 mg/L. j.forsciint.2018.08.044
Alcohol: Co-present in both documented fatal cases (ethanol 0.6–1.4 g/L)supported
blood ethanol 1.4 g/L ante-mortem. j.forsciint.2014.10.016
The case involving concurrent 3-MMC ingestion resulted in fatality.supported
Patient took ~500 mg 3-MMC and ~400 mg 5-APB with ~80g ethanol. Died ~4h after use. j.forsciint.2014.10.016
CYP3A4 modulators: Given that CYP3A4 mediates toxic activation of 5-APB, co-administered CYP3A4 inducers could theoretically amplify hepatotoxicitysupported
CYP3A4 involved in toxic metabolism. s00204-019-02638-9
Cardiac conditions: Any pre-existing valvular disease, cardiac arrhythmia, or condition predisposing to cardiac fibrosis represents an absolute contraindication given the potent 5-HT₂B agonism.supported
Both confirmed as potent full agonists at 5-HT2B receptors. j.ejphar.2012.12.006
Cardiac conditions: Any pre-existing valvular disease, cardiac arrhythmia, or condition predisposing to cardiac fibrosis represents an absolute contraindication given the potent 5-HT₂B agonism.supported
5-HT2B receptor activation identified as cardiac risk. bph.13128
Hepatic impairment: 5-APB's demonstrated hepatotoxicity via CYP3A4-mediated activation makes pre-existing liver disease an absolute contraindicationsupported
CYP3A4 involved in toxic metabolism. Oxidative stress, mitochondrial disruption, apoptosis and necrosis observed. s00204-019-02638-9
Seizure disorders: Seizures are documented in acute 5-APB intoxicationsupported
Clinical: agitation, seizures, hypertension, tachycardia, hyperthermia, bradycardia. j.forsciint.2014.10.016
pharmacology14 · 14 ok
5-APB is classified as a substrate-type monoamine releasing agent (MARA) — it reverses monoamine transporters rather than simply blocking reuptake, causing net efflux of serotonin, dopamine, and norepinephrine into the synaptic cleftsupported
Benzofurans acted as indirect monoamine agonists interacting with transporters similarly to MDMA. bph.13128
5-APB is classified as a substrate-type monoamine releasing agent (MARA) — it reverses monoamine transporters rather than simply blocking reuptake, causing net efflux of serotonin, dopamine, and norepinephrine into the synaptic cleftsupported
Both compounds interact with monoamine transporters and 5-HT receptors in transfected cells; in vivo animal model confirming stimulant-entactogen properties. s00213-020-05648-z
Beyond transporter reversal, 5-APB acts as a direct agonist at 5-HT₂A, 5-HT₂B, and 5-HT₂C receptors, with activity exceeding that of MDMA at all three subtypes. 5-APB is a potent full agonist at 5-HT₂B with affinity below 100 nM — the receptor subtype mechanistically responsible for drug-induced cardiac valvulopathy, as established in the fenfluramine and methysergide literature.partially supported
5-APB showed significant agonist activity at 5-HT2a,b,c receptors... High binding affinities for 5-HT2a,b,c and NEα2 receptors. s00210-016-1297-4
Beyond transporter reversal, 5-APB acts as a direct agonist at 5-HT₂A, 5-HT₂B, and 5-HT₂C receptors, with activity exceeding that of MDMA at all three subtypes. 5-APB is a potent full agonist at 5-HT₂B with affinity below 100 nM — the receptor subtype mechanistically responsible for drug-induced cardiac valvulopathy, as established in the fenfluramine and methysergide literature.partially supported
5-APB and 6-APB showed <100 nM affinity for 5-HT2B and alpha2C receptors. Both confirmed as potent full agonists at 5-HT2B receptors. j.ejphar.2012.12.006
Beyond transporter reversal, 5-APB acts as a direct agonist at 5-HT₂A, 5-HT₂B, and 5-HT₂C receptors, with activity exceeding that of MDMA at all three subtypes. 5-APB is a potent full agonist at 5-HT₂B with affinity below 100 nM — the receptor subtype mechanistically responsible for drug-induced cardiac valvulopathy, as established in the fenfluramine and methysergide literature.supported
Systematic review of 5-HT2B receptor agonism and cardiac valvulopathy. Both LSD and MDMA have high affinity for 5-HT2B and promote downstream fibrotic signaling. a-2794-6487
Beyond transporter reversal, 5-APB acts as a direct agonist at 5-HT₂A, 5-HT₂B, and 5-HT₂C receptors, with activity exceeding that of MDMA at all three subtypes. 5-APB is a potent full agonist at 5-HT₂B with affinity below 100 nM — the receptor subtype mechanistically responsible for drug-induced cardiac valvulopathy, as established in the fenfluramine and methysergide literature.supported
Also interacted with 5-HT receptors. 5-HT2B receptor activation identified as cardiac risk. bph.13128
5-APB also emerged as a potent and selective MAO-A inhibitor in the screening battery of Shimshoni et al. This finding is documented at abstract level only — specific IC₅₀ values were not availablesupported
MDMA analogues including 5-APB emerged as potent MAO-A inhibitors. s00210-016-1297-4
At concentrations estimated during recreational use, additional targets include dopamine receptors, α- and β-adrenergic receptors, GABA_A receptors, and nicotinic acetylcholine receptorssupported
Additional targets including DA receptors, adrenergic receptors, GABAA, ACh receptors may contribute to clinical effects. j.pharmthera.2017.10.022
The net pharmacological fingerprint — serotonin-preferring monoamine release combined with direct 5-HT₂ agonism and MAO-A inhibition — places 5-APB closer to MDA than to MDMA in vivo, as confirmed by microdialysis in male rats.supported
5-APB and 6-APB mimic MDA effects on monoamine transmission in male rats. s00213-020-05648-z
Elimination half-life: The closest analog with published human PK data is 5-MAPB (N-methyl-5-APB), which demonstrated a t₁/₂ of 6.5 hours following first-order kinetics in a confirmed clinical case — described as comparable to the half-life of MDMAsupported
5-MAPB t1/2: 6.5h. Toxicity profile similar to 5-APB and MDMA. j.annemergmed.2016.03.042
Metabolism: 5-APB is itself a primary metabolite of 5-MAPB, formed via N-demethylationsupported
5-APB (N-demethylated product of 5-MAPB) cytotoxicity in rat hepatocytes. 5-MAPB metabolized to 5-APB: ~50 µM 5-APB detected after 3h incubation. jat.3351
Metabolism: 5-APB is itself a primary metabolite of 5-MAPB, formed via N-demethylationsupported
5-APB noted as metabolic demethylation product of 5-MAPB; may contribute to acute 5-HT toxicity and lethal intoxication in mice. jts.41.329
Metabolic pathways characterized for the 6-isomer series (6-APB, 6-MAPB) include N-demethylation mediated by CYP1A2, CYP2D6, and CYP3A4, followed by ring hydroxylation and glucuronide conjugationpartially supported
CYP1A2, CYP2D6, CYP3A4 involved in N-demethylation of 6-MAPB to 6-APB. Main metabolite of 6-APB: 4-carboxymethyl-3-hydroxy amphetamine. s00216-015-8552-2
Co-incubation of primary hepatocytes with CYP3A4 inhibitors attenuated cytotoxicity, demonstrating that Phase I metabolism generates reactive intermediates that contribute to hepatotoxicity rather than representing a detoxification pathway.supported
CYP3A4 involved in toxic metabolism. Oxidative stress, mitochondrial disruption, apoptosis and necrosis observed. s00204-019-02638-9
summary12 · 12 ok
5-(2-Aminopropyl)benzofuran (5-APB) is a synthetic entactogen-stimulant of the aminoalkylbenzofuran class, with a pharmacological profile most closely resembling MDA rather than MDMAsupported
5-APB and 6-APB mimic MDA effects on monoamine transmission in male rats. Both compounds interact with monoamine transporters and 5-HT receptors in transfected cells; in vivo animal model confirming stimulant-entactogen properties. s00213-020-05648-z
5-(2-Aminopropyl)benzofuran (5-APB) is a synthetic entactogen-stimulant of the aminoalkylbenzofuran class, with a pharmacological profile most closely resembling MDA rather than MDMApartially supported
Benzofurans acted as indirect monoamine agonists interacting with transporters similarly to MDMA. bph.13128
The definitive in vitro pharmacological characterization was published by Rickli et al. in 2015, with in vivo confirmation of its MDA-like monoamine transmission profile by Brandt et al. in 2020.supported
Benzofurans pharmacologically characterized in vitro. Benzofurans acted as indirect monoamine agonists interacting with transporters similarly to MDMA. Also interacted with 5-HT receptors. 5-HT2B receptor activation identified as cardiac risk. bph.13128
The definitive in vitro pharmacological characterization was published by Rickli et al. in 2015, with in vivo confirmation of its MDA-like monoamine transmission profile by Brandt et al. in 2020.supported
5-APB and 6-APB mimic MDA effects on monoamine transmission in male rats. Both compounds interact with monoamine transporters and 5-HT receptors in transfected cells; in vivo animal model confirming stimulant-entactogen properties. s00213-020-05648-z
5-APB functions as a substrate-type monoamine releasing agent at DAT, NET, and SERT with submicromolar transporter affinity, a direct agonist at 5-HT₂A/B/C receptors with activity exceeding MDMA at these sites, and a potent MAO-A inhibitorpartially supported
5-APB submicromolar inhibitor of all three monoamine transporters (DAT, NET, SERT). 5-APB and 6-APB showed <100 nM affinity for 5-HT2B and alpha2C receptors. Both confirmed as potent full agonists at 5-HT2B receptors. j.ejphar.2012.12.006
5-APB functions as a substrate-type monoamine releasing agent at DAT, NET, and SERT with submicromolar transporter affinity, a direct agonist at 5-HT₂A/B/C receptors with activity exceeding MDMA at these sites, and a potent MAO-A inhibitorpartially supported
5-APB showed significant agonist activity at 5-HT2a,b,c receptors and significant 5-HT, DA, NE uptake inhibition. MDMA analogues including 5-APB emerged as potent MAO-A inhibitors. s00210-016-1297-4
5-APB functions as a substrate-type monoamine releasing agent at DAT, NET, and SERT with submicromolar transporter affinity, a direct agonist at 5-HT₂A/B/C receptors with activity exceeding MDMA at these sites, and a potent MAO-A inhibitorpartially supported
5-APB showed significant agonist activity at 5-HT2a,b,c receptors and significant 5-HT, DA, NE uptake inhibition. MDMA analogues including 5-APB emerged as potent MAO-A inhibitors. s00210-016-1297-4
The highest-priority safety signal is potent full agonism at 5-HT₂B receptors (<100 nM), the established mechanism for drug-induced cardiac valvulopathy — though no human echocardiographic data exist for 5-APB userssupported
5-APB and 6-APB showed <100 nM affinity for 5-HT2B and alpha2C receptors. Both confirmed as potent full agonists at 5-HT2B receptors. j.ejphar.2012.12.006
The highest-priority safety signal is potent full agonism at 5-HT₂B receptors (<100 nM), the established mechanism for drug-induced cardiac valvulopathy — though no human echocardiographic data exist for 5-APB userssupported
5-HT2B receptor activation identified as cardiac risk. bph.13128
In vitro, 5-APB is more hepatotoxic than its 6-isomer (EC₅₀ 964 µM in primary rat hepatocytes)supported
In vitro hepatotoxicity: 5-APB EC50 HepaRG 2.62 mM, HepG2 3.79 mM, primary rat hepatocytes 964 µM. ... 5-APB more hepatotoxic than 6-APB isomer. s00204-019-02638-9
Two published fatalities bracket post-mortem blood concentrations between 0.86 mg/L and 5.6 mg/Lsupported
Post-mortem femoral blood: 5-APB 0.86 mg/L... Second reported fatal concentration; lower than previously reported. j.forsciint.2018.08.044
Two published fatalities bracket post-mortem blood concentrations between 0.86 mg/L and 5.6 mg/Lsupported
Post-mortem blood: 3-MMC 1.6 µg/mL, 5-APB 5.6 µg/mL, blood ethanol 1.4 g/L ante-mortem. j.forsciint.2014.10.016
comparative-pharmacology8 · 8 ok
In vivo microdialysis in male rats demonstrated that 5-APB and 6-APB mimic MDA rather than MDMA on monoamine transmission patternssupported
5-APB and 6-APB mimic MDA effects on monoamine transmission in male rats. s00213-020-05648-z
In rat drug discrimination paradigms, 5-APB fully substituted for MDMA as a discriminative stimulus but only partially or did not substitute for methamphetamine, cocaine, or DOM (a serotonergic hallucinogen)supported
5-APB fully substituted for MDMA discriminative stimulus, but only partially or not at all for methamphetamine, cocaine, and DOM. j.drugalcdep.2017.07.041
5-APB displays higher activity at 5-HT₂A/B/C receptors than MDMA in comparative assays, and is a potent MAO-A inhibitor — a property not shared by MDMApartially supported
5-APB showed significant agonist activity at 5-HT2a,b,c receptors... MDMA analogues including 5-APB emerged as potent MAO-A inhibitors. s00210-016-1297-4
5-APB displays higher activity at 5-HT₂A/B/C receptors than MDMA in comparative assays, and is a potent MAO-A inhibitor — a property not shared by MDMApartially supported
5-APB showed significant agonist activity at 5-HT2a,b,c receptors... MDMA analogues including 5-APB emerged as potent MAO-A inhibitors. s00210-016-1297-4
Both isomers mimic MDA in vivo, but the hepatotoxicity differential suggests the 5-position substitution alters metabolic activation pathwayssupported
5-APB and 6-APB mimic MDA effects on monoamine transmission in male rats. s00213-020-05648-z
The relative potencies at monoamine transporters and serotonin receptors between the two isomers are documented in Rickli et al. but specific comparative values were not extractable during this research session.supported
Benzofurans pharmacologically characterized in vitro. Benzofurans acted as indirect monoamine agonists interacting with transporters similarly to MDMA. Also interacted with 5-HT receptors. bph.13128
Rudin et al. characterized the (2-aminopropyl)benzo[β]thiophene (APBT) series — sulphur analogues of the APB benzofurans — and found that APBTs lack stimulant effects but display psychedelic-like activity in micesupported
Thio-analogs of benzofuran APBs (APBTs) characterized; comparative pharmacology with 5-APB/6-APB class; monoamine transporter binding profiles and psychedelic-like activity in mice. s41386-021-01221-0
In mouse corpus striatum microdialysis, benzofurans including 5-APB (as demethylation product of 5-MAPB) strongly increase extracellular serotonin more than dopamine, with a 5-HT:DA ratio similar to or exceeding MDMAsupported
Microdialysis in mouse striatum: benzofurans increased extracellular 5-HT more than DA, analogous to MDMA. 5-APB noted as metabolic demethylation product of 5-MAPB. jts.41.329
pharmacokinetic-detail7 · 6 ok
5-APB occupies a dual metabolic role: it is both an administered parent compound and a primary metabolite of 5-MAPB (N-methyl-5-APB), formed via CYP-mediated N-demethylationsupported
5-APB (N-demethylated product of 5-MAPB) cytotoxicity in rat hepatocytes. 5-MAPB metabolized to 5-APB: ~50 µM 5-APB detected after 3h incubation. jat.3351
5-APB occupies a dual metabolic role: it is both an administered parent compound and a primary metabolite of 5-MAPB (N-methyl-5-APB), formed via CYP-mediated N-demethylationsupported
5-APB noted as metabolic demethylation product of 5-MAPB; may contribute to acute 5-HT toxicity and lethal intoxication in mice. jts.41.329
This complicates forensic interpretation when 5-APB is detected post-mortem, as its presence may reflect direct ingestion or metabolic conversion from 5-MAPB or 5-EAPB.supported
Fatal case involving 5-EAPB and MDAI. Also detected: 5-MAPB and 5-APB in blood (5-APB: 0.546 mg/L) and urine. Demonstrates co-occurrence of 5-APB as metabolite/adulterant in benzofuran-related deaths. j.forsciint.2019.03.023
Welter et al. identified the following Phase I and Phase II pathways for 6-APB and 6-MAPB: N-demethylation (CYP1A2, CYP2D6, CYP3A4), hydroxylation of the benzofuran ring system, and glucuronide conjugation of hydroxylated metabolitespartially supported
CYP1A2, CYP2D6, CYP3A4 involved in N-demethylation of 6-MAPB to 6-APB. Main metabolite of 6-APB: 4-carboxymethyl-3-hydroxy amphetamine. s00216-015-8552-2
The closest pharmacokinetic reference is 5-MAPB, for which Hofer et al. documented first-order elimination with a t₁/₂ of 6.5 hours in a clinical intoxication casesupported
5-MAPB t1/2: 6.5h. j.annemergmed.2016.03.042
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
Welter et al. developed validated methods to differentiate 5-APB from 6-APB in urine by GC-MS following heptafluorobutyrylation, addressing a forensic challenge given their identical molecular weightssupported
5-APB/5-MAPB differentiated from 6-isomers by GC-MS after heptafluorobutyrylation. s00216-015-8552-2
receptor-pharmacology7 · 7 ok
5-APB is a submicromolar inhibitor of all three monoamine transporters (DAT, NET, SERT), with higher potency at serotonin-preferring targets relative to pure stimulantssupported
5-APB submicromolar inhibitor of all three monoamine transporters (DAT, NET, SERT). j.ejphar.2012.12.006
Zwartsen et al. measured IC₅₀ values for 5-APB at DAT, NET, and SERT using a high-throughput fluorescence-based transporter assay, reporting values generally consistent with prior radiometric assayssupported
Fluorescent assay for monoamine transporter inhibition. 5-APB tested; IC50 values derived. Most IC50 values in line with previous radiometric assays. j.tiv.2017.05.010
Molecular docking studies by Sahai et al. demonstrated that 5-APB binds at the S1 (primary binding) site of the dopamine transporter, overlapping with the binding modes of dopamine, cocaine, and amphetaminesupported
Molecular docking: 5-MAPB and 5-APB bind DAT at S1 site, overlapping with dopamine, cocaine, amphetamine binding modes. j.pnpbp.2016.11.004
5-HT₂B: Affinity below 100 nM; confirmed as a potent full agonist. This is the highest-priority cardiac safety signal.supported
5-APB and 6-APB showed <100 nM affinity for 5-HT2B and alpha2C receptors. Both confirmed as potent full agonists at 5-HT2B receptors. j.ejphar.2012.12.006
5-HT₂C: Significant agonist activity, exceeding MDMA at this subtype.partially supported
5-APB showed significant agonist activity at 5-HT2a,b,c receptors. s00210-016-1297-4
The elevated 5-HT₂A/B/C activity relative to MDMA positions 5-APB pharmacologically between classical entactogens and serotonergic psychedelics — consistent with the MDA-like classification observed in vivo.supported
5-APB and 6-APB mimic MDA effects on monoamine transmission in male rats. Both compounds interact with monoamine transporters and 5-HT receptors in transfected cells. s00213-020-05648-z
Shimshoni et al. identified 5-APB as a potent and selective MAO-A inhibitor when screened against a comprehensive receptor, transporter, and enzyme batterysupported
5-APB, 6-MAPB, 5-MAPB screened as potential anti-PTSD drugs... MDMA analogues including 5-APB emerged as potent MAO-A inhibitors. s00210-016-1297-4
clinical-evidence5 · 5 ok
Post-mortem blood concentration: 5-APB 5.6 µg/mL (5,600 ng/mL); 3-MMC 1.6 µg/mL; ante-mortem serum ethanol 1.4 g/Lsupported
Post-mortem blood: 3-MMC 1.6 µg/mL, 5-APB 5.6 µg/mL, blood ethanol 1.4 g/L ante-mortem. j.forsciint.2014.10.016
Post-mortem femoral blood: 5-APB 0.86 mg/L (860 ng/mL); ethanol 0.6 g/L; THC 0.0024 mg/Lsupported
Post-mortem femoral blood: 5-APB 0.86 mg/L, ethanol 0.6 g/L, THC 0.0024 mg/L. j.forsciint.2018.08.044
Case 3 (Deville et al., 2019): Fatal case primarily attributed to 5-EAPB and MDAI; 5-APB detected in blood at 0.546 mg/L and in urine. 5-APB was likely present as a demethylation metabolite of 5-EAPB or as a separate co-ingestant.supported
Fatal case involving 5-EAPB and MDAI. Also detected: 5-MAPB and 5-APB in blood (5-APB: 0.546 mg/L) and urine. Demonstrates co-occurrence of 5-APB as metabolite/adulterant in benzofuran-related deaths. j.forsciint.2019.03.023
Shimshoni et al. screened 5-APB as part of a panel of MDMA benzofuran analogues evaluated for potential anti-PTSD applications, motivated by the clinical success of MDMA-assisted psychotherapysupported
5-APB, 6-MAPB, 5-MAPB screened as potential anti-PTSD drugs. s00210-016-1297-4
Barceló et al. (2017) reported a patient presenting to the emergency department with confirmed exposure to 5-MAPB, 5-APB, 5-EAPB, and ethylphenidate who recovered with supportive treatment. 5-APB was quantified in serum, urine, and hair — the hair analysis confirming a pattern of repeated use.supported
Case: acute intoxication patient tested positive for 5-MAPB, 5-APB, 5-EAPB, ethylphenidate. Confirmed in urine, serum, and hair by GC-MS and UHPLC-MS/MS. Hair samples confirmed repeated use. s00414-017-1648-9
neuroscience4 · 4 ok
The dopaminergic component (DAT reversal) activates mesolimbic reward circuitry (ventral tegmental area to nucleus accumbens), contributing to stimulant and reinforcing propertiessupported
Dopamine signaling in nucleus accumbens central to reinforcing properties. Evidence base for addictive potential of amphetamine-like stimulants. fnins.2016.00153
5-APB's elevated 5-HT₂A agonism relative to MDMA predicts greater engagement of cortical 5-HT₂A receptors on layer V pyramidal neurons — the cellular trigger for psychedelic-like perceptual effectssupported
5-APB showed significant agonist activity at 5-HT2a,b,c receptors... High binding affinities for 5-HT2a,b,c and NEα2 receptors. s00210-016-1297-4
The serotonin-preferring ratio predicts stronger hedonic and empathogenic effects than pure stimulants, while retaining meaningful reward pathway activation — consistent with observed moderate abuse potential.supported
Review of rewarding and addictive properties of NPS including MDMA analogs (benzofurans). Dopamine signaling in nucleus accumbens central to reinforcing properties. fnins.2016.00153
Memory reconsolidation: MDMA's therapeutic mechanism in PTSD treatment is hypothesized to involve facilitated fear memory reconsolidation under reduced amygdala reactivity. 5-APB's pharmacological profile — serotonin release, 5-HT₂ agonism, empathogenic phenomenology — is compatible with this framework, which motivated its inclusion in Shimshoni et al.'s screening panel of potential anti-PTSD compounds.supported
5-APB, 6-MAPB, 5-MAPB screened as potential anti-PTSD drugs. 5-APB showed significant agonist activity at 5-HT2a,b,c receptors and significant 5-HT, DA, NE uptake inhibition. s00210-016-1297-4
history3 · 1 ok
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
The first systematic pharmacological characterization of 5-APB as a novel psychoactive substance appeared in Iversen et al. in 2013, with Rickli et al. in 2015 providing the definitive in vitro receptor and transporter profile.supported
Benzofurans pharmacologically characterized in vitro. Benzofurans acted as indirect monoamine agonists interacting with transporters similarly to MDMA. Also interacted with 5-HT receptors. bph.13128