generation run 2026-05-12
61 min completedmodel pipeline-v5plan not recordedrun/4dfbff87…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
- sparse_evidence
- structural_inference
- safety_data_unverified
Reproduce
- inputs
- 23 source keys (listed under Sources)
- plan
- not recorded — template version, prompt hash and git SHA are written from 2026-09 onward
- model
- pipeline-v5
- streams
- none — agent transcripts are persisted from 2026-09 onward
19 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | ClinicalTrials.gov · absence | mexedrone | 0 | 0 | No trials found |
| 2 | PubMed | mephedrone pharmacokinetics human metabolism | 8 | 4 | Mephedrone is the structural analog of mexedrone; its pharmacokinetics inform inference about mexedrone. Cathinone review and drug interaction paper relevant to harm reduction sections. |
| 3 | PubMed | mephedrone mexedrone new psychoactive substance | 1 | 0 | Duplicate results; no new unique papers added |
| 4 | OpenAlex | mexedrone synthetic cathinone | 10 | 5 | Selected highest-cited papers directly covering mexedrone or broadly relevant cathinone pharmacology |
| 5 | PubChem | mexedrone | 1 | 1 | Primary chemical identity verification for mexedrone |
| 6 | PubMed | mexedrone cathinone | 9 | 4 | Directly relevant to mexedrone chemistry, metabolism, and forensic toxicology |
| 7 | PubMed | mexedrone pharmacology | 5 | 5 | All directly relevant to mexedrone pharmacology and clinical data |
| 8 | PubMed (PMID:28075189) | Roberts 2017 mexedrone clinical cases - full abstract via OpenAlex | 1 | 1 | Full clinical data; key safety and subjective effects information |
| 9 | OpenAlex | mexedrone monoamine transporter dopamine serotonin | 8 | 3 | SAR review and molecular docking paper directly address mexedrone pharmacology; user perspectives provides subjective effects context |
| 10 | WebFetch - reagent-tests.uk | — | 1 | 1 | Harm reduction identification data for mexedrone |
| 11 | PubMed | mephedrone pharmacokinetics human metabolism | 8 | 5 | Mephedrone pharmacokinetics and cathinone reviews relevant as structural analog inference |
| 12 | PubChem + McLaughlin 2017 + Camuto 2022 | mexedrone chemical identity and metabolism cross-reference | 3 | 1 | Chemical identity verification |
| 13 | Crossref (verify_doi) | DOI verification McLaughlin 2017 and Roberts 2017 | 2 | 2 | DOI verification for primary mexedrone sources |
| 14 | WebSearch | mexedrone legal status UK US EU Sweden Japan | 10 | 2 | Legal status information not available via PubMed |
| 15 | PubMed | Baumann synthetic cathinone neuropharmacology NIDA | 6 | 2 | Authoritative cathinone pharmacology from NIDA group; SAR context for mexedrone |
| 16 | McLaughlin 2017 vs seed data pharmacological class | mexedrone pharmacological class verification | 1 | 1 | Safety-critical pharmacological classification error in seed data |
| 17 | PubMed | tramadol serotonin syndrome monoamine interaction | 6 | 2 | Critical for explaining mexedrone-tramadol lethal interaction mechanism |
| 18 | PubMed | cathinone stimulant MDMA serotonergic interaction | 3 | 2 | Pharmacological framework for understanding mexedrone's DAT:SERT ratio and serotonergic toxicity risk |
| 19 | WebSearch | mexedrone DEA scheduling United States | 10 | 0 | Legal status gap identified - US status unconfirmed |
86 claims by section — every cited sentence, checked against its source
safety23 · 18 ok
Cardiovascular disease: Mexedrone produces sympathomimetic stimulation (tachycardia documented in 64% of clinical presentations)supported
7/11 tachycardic >100 bpm. 15563650.2016.1271424
The only analytically confirmed human exposure data derive from Roberts et al. (2017), who documented 11 cases at City Hospital, Birminghamsupported
305 cases screened; mexedrone in 11 urine samples. 15563650.2016.1271424
Pieprzyca and colleagues reported mexedrone detection in blood samples from fatal mixed-substance poisoning casessupported
26 fatal and 2 non-fatal cases of SC poisonings. Presents pioneering blood concentration data for mexedrone. bkab119
Tachycardia is the most consistently documented cardiovascular effect (64% in the Birmingham series)supported
7/11 tachycardic >100 bpm. 15563650.2016.1271424
More severe cardiovascular toxicity — including hypertension, arrhythmia, and myocardial ischemia — is characteristic of the broader cathinone class but has not been specifically documented for mexedrone alone.supported
Cardiovascular (tachycardia, hypertension) and psychiatric/neurological adverse effects (agitation, seizures, paranoia, hallucinations). sar.s37257
Claim in safety — inconclusiveinconclusiveworking →
Acute psychosis was documented in 3 of 11 analytically confirmed cases (27%), presenting as hallucinations and delusions with prominent paranoid and supernatural contentsupported
Delusions and hallucinations with paranoia (supernatural/demonic theme) in 3 cases; none had prior psychosis. 15563650.2016.1271424
Anxiety, nervousness, and paranoia are reported across the cathinone class in qualitative user-perspective researchsupported
Adverse effects: anxiety, hallucinations, nervousness, paranoia (nervous system). hup.2610
Jeon and colleagues showed dose-dependent conditioned place preference in mice (10–50 mg/kg, i.p.), dose-dependent self-administration in rats (0.1–0.5 mg/kg/infusion, i.v.), and full substitution for cocaine in drug discrimination paradigms.supported
Mexedrone produced significant conditioned place preference (10-50 mg/kg) and maintained self-administration (0.1-0.5 mg/kg/infusion) in rats. Fully substituted for cocaine discriminative stimulus. j.ejphar.2024.176466
Acute administration produced SERT downregulation in the dorsal striatum, suggesting neuroadaptive changes that may underlie tolerance to serotonergic effectssupported
Decreased SERT levels and elevated 5-HT in dorsal striatum. j.ejphar.2024.176466
The moderate physical and psychological dependence potential attributed to the compound in existing databases is consistent with preclinical evidence and general cathinone-class data but has not been independently validated in human studies.supported
Mexedrone produced significant conditioned place preference (10-50 mg/kg) and maintained self-administration (0.1-0.5 mg/kg/infusion) in rats. j.ejphar.2024.176466
Tramadol: Tramadol inhibits serotonin reuptake via SERT and additionally produces seizure risk through serotonergic mechanisms. Combined with mexedrone's SERT inhibition and weak releasing activity, the serotonergic burden creates risk of severe serotonin syndrome and potentially death. No published case report specifically documenting a mexedrone–tramadol fatality has been identified, but the mechanistic basis is well-established.supported
Tramadol inhibits SERT in human HEK293 cells. Combined with serotonergic drugs (MAOIs, SSRIs, serotonin-releasing agents), tramadol can precipitate serotonin syndrome. s00204-018-2244-6
Tramadol: Tramadol inhibits serotonin reuptake via SERT and additionally produces seizure risk through serotonergic mechanisms. Combined with mexedrone's SERT inhibition and weak releasing activity, the serotonergic burden creates risk of severe serotonin syndrome and potentially death. No published case report specifically documenting a mexedrone–tramadol fatality has been identified, but the mechanistic basis is well-established.partially supported
Tramadol-induced seizures are mainly related to GABAergic pathway, not serotonergic. Tramadol still increases brain serotonin and norepinephrine. ph15101254
Tramadol: Tramadol inhibits serotonin reuptake via SERT and additionally produces seizure risk through serotonergic mechanisms. Combined with mexedrone's SERT inhibition and weak releasing activity, the serotonergic burden creates risk of severe serotonin syndrome and potentially death. No published case report specifically documenting a mexedrone–tramadol fatality has been identified, but the mechanistic basis is well-established.supported
Tramadol inhibits SERT in human HEK293 cells. Combined with serotonergic drugs (MAOIs, SSRIs, serotonin-releasing agents), tramadol can precipitate serotonin syndrome. s00204-018-2244-6
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
SSRIs/SNRIs: Additive serotonergic activity creates dose-dependent serotonin syndrome risk.supported
Serotonergic interactions with SSRIs/MAOIs. ftd.0000000000000682
Pharmacokinetic interactions: CYP2C19 inhibitors (omeprazole, fluoxetine, fluvoxamine) may substantially increase mexedrone plasma concentrations by impairing metabolic clearancesupported
Key CYPs: CYP2C19 (primary), CYP2D6 and CYP1A2. dta.3179
Claim in safety — not_supportednot supportedworking →
Pre-existing cardiac conditions — hypertension, arrhythmia, coronary artery disease, structural heart defects — represent absolute contraindications given the absence of controlled safety data and the sympathomimetic mechanism of all cathinone-class compounds.supported
Cardiovascular (tachycardia, hypertension) and psychiatric/neurological adverse effects (agitation, seizures, paranoia, hallucinations). sar.s37257
Psychiatric vulnerability: Acute psychosis occurred in 27% of confirmed cases, in patients without prior psychiatric historysupported
Delusions and hallucinations with paranoia (supernatural/demonic theme) in 3 cases; none had prior psychosis. 15563650.2016.1271424
This is an absolute contraindication for MAOI users and a strong relative contraindication for SSRI/SNRI users.supported
Serotonergic interactions with SSRIs/MAOIs. Monoamine-based interactions relevant to mexedrone drug interaction profile. ftd.0000000000000682
Claim in safety — inconclusiveinconclusiveworking →
pharmacology16 · 11 ok
The experimental potency trends across transporters were successfully reproduced computationally for mexedrone, validating the docking model.supported
Experimental potency trends for mexedrone reproduced computationally. acsomega.0c01370
Claim in pharmacology — inconclusiveinconclusiveworking →
At SERT, mexedrone displays weak releasing activity with an EC₅₀ of 2.5 µM — the only transporter at which it functions as a releaser.supported
Devoid of releasing activity at DAT and NET but displayed weak releasing activity at SERT (EC50 = 2.5 uM). dta.2053
Claim in pharmacology — not_supportednot supportedworking →
McLaughlin et al. (2017) explicitly demonstrated that mexedrone is devoid of releasing activity at DAT and NETsupported
Devoid of releasing activity at DAT and NET but displayed weak releasing activity at SERT (EC50 = 2.5 uM). dta.2053
Molecular docking studies demonstrate that mexedrone preferentially binds the S1 (central) binding site of DAT, NET, and SERT — the same site occupied by classical monoamine reuptake inhibitorssupported
All three substances preferred the S1 or central binding site regardless of transporter. acsomega.0c01370
5-HT₂A receptors: Locomotor stimulation produced by mexedrone in mice is mediated at least in part through the 5-HT₂A receptor. Pre-treatment with the selective 5-HT₂A antagonist M100907 (0.5–1.0 mg/kg) fully reversed mexedrone-induced hyperlocomotion.supported
Mexedrone increased locomotor activity reversed by 5-HT2A antagonist M100907. j.ejphar.2024.176466
Claim in pharmacology — not_supportednot supportedworking →
Claim in pharmacology — not_supportednot supportedworking →
In vitro Phase I metabolic profiling using human liver microsomes (HLM) and recombinant CYP450 isoforms identified three primary metabolic pathways:supported
In vitro Phase I metabolism using human liver microsomes and recombinant CYP450. Main reactions: hydroxylation and N- and O-dealkylation. dta.3179
CYP2C19 is the principal metabolizing enzyme, responsible for both hydroxylation and dealkylation reactionssupported
Main reactions: hydroxylation and N- and O-dealkylation. Key CYPs: CYP2C19 (primary), CYP2D6 and CYP1A2. dta.3179
This contrasts with the parent compound mephedrone, for which CYP2D6 is the primary metabolizing enzyme in humanssupported
Linear kinetics; CYP2D6 mediates mephedrone metabolism. Poor metabolizers at risk of acute toxicity. cpt.1417
Claim in pharmacology — inconclusiveinconclusiveworking →
A significant fraction of administered mexedrone is excreted unchanged, and hydroxylated metabolites serve as recommended markers of intake for forensic detection.supported
Best markers of intake: mexedrone unchanged and hydroxylated metabolites. dta.3179
Lenzi and colleagues evaluated mexedrone's genotoxic potential using the micronucleus assay in TK6 lymphoblastoid cellssupported
Mexedrone demonstrated mutagenic potential in TK6 cells at 35-100 uM in micronucleus assay. ijms22126320
The genotoxic mechanism is not mediated by reactive oxygen species (ROS): no statistically significant increase in ROS was observed at tested concentrationssupported
No significant ROS increase. Mutagenicity not mediated by ROS. ijms22126320
summary10 · 8 ok
It functions as a weak non-selective monoamine reuptake inhibitor with additional weak serotonin-releasing activity (SERT EC₅₀ = 2.5 µM), producing mild stimulant effects over a 4–6 hour oral durationsupported
Mexedrone was a weak non-selective uptake blocker with IC50 values in the low uM range. Devoid of releasing activity at DAT and NET but displayed weak releasing activity at SERT (EC50 = 2.5 uM). dta.2053
Mexedrone first appeared on UK research chemical markets in August 2015, designed to circumvent existing cathinone scheduling controlspartially supported
Mexedrone appeared in 2015, advertised by UK Internet retailers as a non-controlled mephedrone derivative. dta.2053
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Two independent analytical characterizations were published in 2016–2017, followed by the first and only clinically confirmed case series of human exposuressupported
305 cases screened; mexedrone in 11 urine samples. 15563650.2016.1271424
Mexedrone weakly inhibits reuptake at all three monoamine transporters (DAT, NET, SERT) with IC₅₀ values in the low micromolar range, but — unlike mephedrone — is devoid of releasing activity at DAT and NETsupported
Mexedrone was a weak non-selective uptake blocker with IC50 values in the low uM range. Devoid of releasing activity at DAT and NET but displayed weak releasing activity at SERT (EC50 = 2.5 uM). dta.2053
Locomotor effects in mice are mediated in part through 5-HT₂A receptors, as demonstrated by reversal with the selective antagonist M100907supported
Mexedrone increased locomotor activity reversed by 5-HT2A antagonist M100907. j.ejphar.2024.176466
Cardiovascular toxicity (tachycardia in 7 of 11 confirmed cases) and acute psychosis (hallucinations with paranoid content in 3 of 11 cases, absent prior psychiatric history) represent the primary acute riskssupported
7/11 tachycardic >100 bpm. Delusions and hallucinations with paranoia (supernatural/demonic theme) in 3 cases; none had prior psychosis. 15563650.2016.1271424
In vitro mutagenicity has been demonstrated at concentrations of 35–100 µM, though clinical relevance at recreational doses is unknownsupported
Mexedrone demonstrated mutagenic potential in TK6 cells at 35-100 uM in micronucleus assay. ijms22126320
CYP2C19 polymorphism may produce significant interindividual variability in plasma concentrationssupported
Key CYPs: CYP2C19 (primary), CYP2D6 and CYP1A2. dta.3179
neuroscience9 · 8 ok
The preclinical demonstration of conditioned place preference (10–50 mg/kg, i.p., in mice) and intravenous self-administration (0.1–0.5 mg/kg/infusion in rats) confirms that mexedrone engages reward circuitry sufficiently to maintain reinforcing behavior.supported
Mexedrone produced significant conditioned place preference (10-50 mg/kg) and maintained self-administration (0.1-0.5 mg/kg/infusion) in rats. j.ejphar.2024.176466
Claim in neuroscience — inconclusiveinconclusiveworking →
Acute mexedrone (50 mg/kg) decreased SERT protein levels in the dorsal striatal synaptosome fraction, indicating SERT downregulation — a neuroadaptive response consistent with sustained serotonergic stimulation.supported
Decreased SERT levels and elevated 5-HT in dorsal striatum. j.ejphar.2024.176466
Weak SERT releasing activity (EC₅₀ = 2.5 µM) drives extracellular serotonin elevation.supported
Devoid of releasing activity at DAT and NET but displayed weak releasing activity at SERT (EC50 = 2.5 uM). dta.2053
The selective 5-HT₂A antagonist M100907 fully reversed mexedrone-induced locomotor stimulation, establishing 5-HT₂A receptor activation as a necessary component of at least the locomotor effects.supported
Mexedrone increased locomotor activity reversed by 5-HT2A antagonist M100907. j.ejphar.2024.176466
The DAT:SERT selectivity ratio framework predicts that compounds with relatively greater serotonergic activity (lower DAT:SERT ratio) produce less compulsive reinforcement and more empathogenic/entactogenic character than dopamine-dominant stimulantssupported
DAT:SERT ratio predicts stimulant vs entactogen profile and toxicity. Serotonergic drugs associated with serotonin syndrome, hyperthermia, seizures, hyponatremia. Dopaminergic drugs are highly addictive. smw.2015.14043
The preclinical self-administration data confirm that reinforcement occurs but do not allow comparison of reinforcement magnitude with mephedrone.supported
Mexedrone produced significant conditioned place preference (10-50 mg/kg) and maintained self-administration (0.1-0.5 mg/kg/infusion) in rats. j.ejphar.2024.176466
SERT downregulation following acute mexedrone suggests that serotonergic effects may undergo rapid tolerance, while dopaminergic effects — mediated by a reuptake inhibition mechanism rather than releasing — may follow a different tolerance trajectorysupported
Decreased SERT levels and elevated 5-HT in dorsal striatum. j.ejphar.2024.176466
Does SERT downregulation persist with repeated use? The acute SERT reduction observed by Jeon et al. after a single dose raises the question of whether chronic use produces lasting serotonergic deficits analogous to those documented for MDMA and mephedrone.supported
Decreased SERT levels and elevated 5-HT in dorsal striatum. j.ejphar.2024.176466
receptor-pharmacology6 · 5 ok
5-HT₂A: Functional involvement confirmed by antagonist reversal — M100907 (0.5–1.0 mg/kg, i.p.) fully reversed mexedrone-induced locomotor stimulation in mice. No Ki value has been reported.supported
Mexedrone increased locomotor activity reversed by 5-HT2A antagonist M100907. j.ejphar.2024.176466
Mexedrone interacts with all three monoamine transporters as a reuptake inhibitor with IC₅₀ values in the low micromolar rangesupported
Mexedrone was a weak non-selective uptake blocker with IC50 values in the low uM range. dta.2053
At SERT, mexedrone additionally acts as a weak substrate-type releaser (EC₅₀ = 2.5 µM).supported
Devoid of releasing activity at DAT and NET but displayed weak releasing activity at SERT (EC50 = 2.5 uM). dta.2053
The compound displays no releasing activity at DAT or NET at any tested concentrationsupported
Devoid of releasing activity at DAT and NET but displayed weak releasing activity at SERT (EC50 = 2.5 uM). dta.2053
Claim in receptor-pharmacology — not_supportednot supportedworking →
Senior and colleagues performed computational molecular docking of mexedrone at all three monoamine transporterssupported
Molecular docking study of MDAI, mexedrone, and phenibut at DAT, NET, and SERT. acsomega.0c01370
comparative-pharmacology5 · 5 ok
Mephedrone is a potent substrate-type releasing agent at all three monoamine transporters (DAT, NET, SERT), acting as a true amphetamine-like releaser that drives vesicular monoamine effluxsupported
4-methylmethcathinone releases NE, DA, and 5-HT. j.euroneuro.2014.12.012
Mephedrone is a potent substrate-type releasing agent at all three monoamine transporters (DAT, NET, SERT), acting as a true amphetamine-like releaser that drives vesicular monoamine effluxsupported
Ring-substituted cathinones like mephedrone are transporter substrates (releasers)... All increase extracellular monoamines. 164_2018_178
Metabolically, the compounds also diverge: mephedrone is primarily metabolized by CYP2D6, while mexedrone shifts to CYP2C19 as the principal enzymesupported
Linear kinetics; CYP2D6 mediates mephedrone metabolism. cpt.1417
Metabolically, the compounds also diverge: mephedrone is primarily metabolized by CYP2D6, while mexedrone shifts to CYP2C19 as the principal enzymesupported
Key CYPs: CYP2C19 (primary), CYP2D6 and CYP1A2. dta.3179
Nadal-Gratacós and colleagues reviewed structure-activity relationships across the synthetic cathinone class, contextualizing mexedrone's alpha-methoxy modification within the broader SAR landscapesupported
Comprehensive updated SAR review covering 209+ synthetic cathinones reported to UNODC. Relevant to understanding how methoxy group at alpha-carbon affects mexedrone's pharmacological profile vs mephedrone. acsptsci.4c00299
history5 · 4 ok
Mexedrone entered the European research chemical market in August 2015, advertised by UK internet retailers as a legal, non-controlled alternative to mephedronepartially supported
Mexedrone appeared in 2015, advertised by UK Internet retailers as a non-controlled mephedrone derivative. dta.2053
Claim in history — inconclusiveinconclusiveworking →
Qian and colleagues performed analytical characterization via LC-QTOF-MS, GC-MS, and NMR spectroscopy, describing their work as "the first report" on the compound's chemical data.supported
First report of analytical characterization of mexedrone. LC-QTOF-MS, GC-MS and NMR spectroscopy. No chemical or pharmacological data had appeared prior to this report. dta.1983
McLaughlin and colleagues published the definitive pharmacological characterization, including full synthesis, spectroscopic analysis, single-crystal X-ray diffraction, and in vitro monoamine transporter assays in rat brain synaptosomes.supported
Full analytical characterization via chromatographic, spectroscopic and mass spectrometric platforms and X-ray crystal structure. Mexedrone was a weak non-selective uptake blocker with IC50 values in the low uM range. dta.2053
Roberts and colleagues published the first analytically confirmed clinical case series in 2017, identifying 11 patients with toxicologically verified mexedrone exposure among 305 cases screened at City Hospital, Birmingham, UKsupported
305 cases screened; mexedrone in 11 urine samples. 15563650.2016.1271424
pharmacokinetic-detail5 · 4 ok
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
Camuto and colleagues characterized Phase I metabolism using human liver microsomes and individual recombinant CYP450 isoforms:supported
In vitro Phase I metabolism using human liver microsomes and recombinant CYP450. dta.3179
This differs from the parent compound mephedrone, which is primarily metabolized by CYP2D6supported
Linear kinetics; CYP2D6 mediates mephedrone metabolism. cpt.1417
Based on CYP2C19 as the primary metabolizing enzyme, the following pharmacokinetic interactions are predicted:supported
Key CYPs: CYP2C19 (primary), CYP2D6 and CYP1A2. dta.3179
For forensic and clinical toxicological purposes, unchanged mexedrone and hydroxylated metabolites are recommended as markers of intakesupported
Best markers of intake: mexedrone unchanged and hydroxylated metabolites. dta.3179
clinical-evidence4 · 3 ok
Pieprzyca and colleagues reported mexedrone detection in mixed-substance poisoning cases, including fatalitiessupported
26 fatal and 2 non-fatal cases of SC poisonings. Presents pioneering blood concentration data for mexedrone. All fatal cases associated with multiple organ failure. Polydrug use increased SC toxicity. bkab119
Mexedrone-specific lethal blood concentrations could not be isolated from the polydrug context in this dataset.supported
All fatal cases associated with multiple organ failure. Polydrug use increased SC toxicity. bkab119
Roberts and colleagues identified 11 patients with toxicologically confirmed mexedrone exposure among 305 cases screened at City Hospital, Birmingham, UK.supported
305 cases screened; mexedrone in 11 urine samples. 15563650.2016.1271424
Claim in clinical-evidence — inconclusiveinconclusiveworking →
chemistry3 · 3 ok
This single structural modification profoundly alters pharmacological activity, abolishing substrate-type releasing activity at the dopamine and norepinephrine transporters while retaining weak reuptake inhibition.supported
Mexedrone was a weak non-selective uptake blocker with IC50 values in the low uM range. Devoid of releasing activity at DAT and NET but displayed weak releasing activity at SERT (EC50 = 2.5 uM). dta.2053
This single structural modification profoundly alters pharmacological activity, abolishing substrate-type releasing activity at the dopamine and norepinephrine transporters while retaining weak reuptake inhibition.supported
Relevant to understanding how methoxy group at alpha-carbon affects mexedrone's pharmacological profile vs mephedrone. acsptsci.4c00299
Despite identical molecular formulae, these isomers display strikingly divergent pharmacology: N-methoxymephedrone is a fully efficacious substrate-type releaser at all three monoamine transporters.supported
N-methoxymephedrone was a fully efficacious releasing agent across all three transporters. dta.2053