generation run 2026-04-26
48 min completedmodel pipeline-v5plan not recordedrun/01526e13…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
none raised on this run
Reproduce
- inputs
- 17 source keys (listed under Sources)
- plan
- not recorded — template version, prompt hash and git SHA are written from 2026-09 onward
- model
- pipeline-v5
- streams
- none — agent transcripts are persisted from 2026-09 onward
19 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | Web Search | 4-AcO-MET legal status scheduling controlled substance UK US Australia | 5 | 2 | — |
| 2 | PubMed · absence | 4-AcO-MET 4-acetoxy-MET tryptamine psychedelic | 0 | — | — |
| 3 | PubMed | PMID 36669875 | 1 | 1 | — |
| 4 | PubMed | psilocin analogs acetoxy tryptamine receptor binding pharmacology | 1 | 1 | Closest 4-acetoxy tryptamine metabolic pathway study to 4-AcO-MET |
| 5 | WebFetch | — | 1 | — | — |
| 6 | PubMed | PMID 26265285 | 1 | 1 | — |
| 7 | OpenAlex | 4-AcO-MET 4-acetoxy-MET tryptamine psychedelic | 10 | 5 | Direct pharmacology, crystal structure, and safety case reports |
| 8 | WebFetch | — | 1 | — | — |
| 9 | PubChem | 4-AcO-MET | 1 | 1 | Primary chemical identity source |
| 10 | PubMed | tramadol serotonin syndrome seizure drug interaction tryptamine | 1 | 1 | — |
| 11 | WebSearch | 4-HO-MET metocin pharmacology synthesis Shulgin TiHKAL first synthesis 1997 | 10 | 2 | — |
| 12 | WebFetch | — | 1 | 1 | — |
| 13 | PubMed | 4-AcO-DMT psilacetin metabolite identification urinary biomarker forensic | 1 | 1 | — |
| 14 | PubMed | Repke tryptamine synthesis hydroxytryptamine 4-hydroxy pharmacology | 1 | 1 | — |
| 15 | WebSearch | 4-AcO-MET Switzerland Verzeichnis E Germany NpSG scheduling controlled | 5 | 1 | — |
| 16 | PubMed | Identification New Psychoactive Tryptamines 4-OH-MET | 1 | 1 | — |
| 17 | PubMed | psychedelic 5-HT2A receptor agonist tolerance rapid tachyphylaxis | 1 | 1 | — |
| 18 | PubMed | in silico toxicity tryptamine psilocin psilocybin O-acetylpsilocin computational | 1 | 1 | — |
| 19 | ClinicalTrials.gov · absence | 4-AcO-MET tryptamine psychedelic | 0 | 0 | — |
48 claims by section — every cited sentence, checked against its source
safety16 · 9 ok
Jurowski et al. performed in silico toxicity assessment of the closest structural analog, 4-AcO-DMT, predicting an oral LD₅₀ in the 100–500 mg/kg range (Cramer Class III, moderate-to-high acute toxicity)supported
In silico toxicology of 6 tryptamines including 4-AcO-DMT. Predicted oral LD50 100-500 mg/kg. Cramer Class III. s00204-026-04365-4
Cardiovascular and gastrointestinal systems were identified as primary predicted target organs (≥90% predicted probability). 4-AcO-DMT was predicted to be non-mutagenic and non-endocrine-activepartially supported
Cardiovascular and GI primary targets. Non-mutagenic predicted. s00204-026-04365-4
Claim in safety — inconclusiveinconclusiveworking →
McIntyre et al. reported a fatality in which 4-HO-MET was detected by GC-MS in postmortem specimenssupported
4-HO-MET (active metabolite of 4-AcO-MET) also detected by GC-MS, not quantified. bkv089
Malaca et al. reviewed tryptamine toxicology broadly, finding that morbidity from novel psychoactive tryptamines is underestimated and that tryptamines are typically absent from standard toxicology screening panelspartially supported
Review of tryptamine toxicology. 22 new analytical methods 2015-2020. Morbidity considerable and underestimated. ijms21239279
Kopra et al. analyzed psychedelic-related fatalities in England, Wales, and Northern Ireland (1997–2022), finding that deaths directly attributable to classical serotonergic psychedelics are rare relative to other drug classes.supported
Systematic characterization of psychedelic-related deaths 1997-2022. Fatalities associated with psychedelics appear rare. j.pnpbp.2024.111177
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
De la Fuente Revenga et al. demonstrated in mice that repeated psychedelic administration produces progressive decreases in head twitch response (a behavioral proxy for psychedelic effect), with single-dose tolerance observable within 24 hourssupported
Repeated psychedelic administration causes progressive HTR decrease. Single-dose tolerance after 24h. acschemneuro.2c00170
Cross-tolerance extends between structurally distinct psychedelics (DOI and LSD were tested), indicating a shared mechanism of 5-HT₂A receptor downregulation in frontal cortex independent of β-arrestin-2.partially supported
Cross-tolerance between DOI and LSD. 5-HT2AR downregulation in frontal cortex. acschemneuro.2c00170
Claim in safety — inconclusiveinconclusiveworking →
{{Warning}}Tramadol: Tramadol inhibits the serotonin transporter (SERT) and has been linked by the FDA to serotonin toxicity risksupported
Tramadol inhibits human SERT in vitro; combined with serotonergic drugs, can precipitate serotonin syndrome. FDA Drug Safety Communication 2016. s00204-018-2244-6
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Contraindication data for 4-AcO-MET are inferred from psilocybin class-level pharmacologysupported
Practical guidance for psilocybin therapy including pharmacology, pharmacokinetics, dosing, contraindications, adverse events, drug interactions. fpsyt.2022.1040217
receptor-pharmacology8 · 6 ok
The 4-substituted compounds demonstrated high selectivity for the 5-HT₂A receptorsupported
4-substituted compounds show high selectivity for 5-HT2AR. jpet.122.001454
The 4-acetoxy and 4-propionoxy analogs displayed somewhat weaker binding affinities than the corresponding 4-hydroxy compounds but maintained similar target profiles across serotonin receptor subtypessupported
4-acetoxy analogues show somewhat weaker binding affinities but similar target profiles to 4-hydroxy compounds. acsptsci.2c00222
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
The foundational selectivity data for 4-hydroxylated tryptamines derives from McKenna et al., who established that this class displays 25–380-fold selectivity for 5-HT₂A over 5-HT₁A in radioligand binding assayssupported
4-hydroxylated derivatives show 25-380-fold selectivity for 5-HT2A vs 5-HT1A. pmid:2139186
Within this class, N,N-dialkyl chain length modulates affinity: short chains (dimethyl, methyl-ethyl) retain high affinity, while bulky substituents (diisopropyl and larger) substantially reduce binding at both 5-HT₂A and 5-HT₁A.supported
N,N-dialkyl size secondary determinant; groups larger than diisopropyl markedly reduce affinity. pmid:2139186
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
{{Info}}Quantitative Ki and EC₅₀ values for 4-AcO-MET at individual receptor targets are known to exist in the Kozell et al. and Glatfelter et al. publications but could not be retrieved during research due to access restrictionssupported
Includes 4-AcO-MET in binding panel. jpet.122.001454
{{Info}}Quantitative Ki and EC₅₀ values for 4-AcO-MET at individual receptor targets are known to exist in the Kozell et al. and Glatfelter et al. publications but could not be retrieved during research due to access restrictionssupported
Includes 4-AcO-MET binding data. acsptsci.2c00222
pharmacology6 · 6 ok
Following oral administration, the acetate ester is expected to undergo rapid hydrolysis by serum esterases to yield the active metabolite 4-HO-METsupported
Primary: hydrolysis to psilocin. dta.3255
This prodrug-to-active-metabolite conversion parallels the established pathway of 4-AcO-DMT to psilocin, for which Zhai et al. demonstrated that ester hydrolysis is the predominant phase I metabolic transformation in pooled human liver microsomessupported
4-AcO-DMT metabolism in pooled human liver microsomes. Primary: hydrolysis to psilocin. dta.3255
McKenna et al. demonstrated in radioligand competition assays that 4-hydroxylated indolealkylamines as a class display 25–380-fold selectivity for the 5-HT₂A receptor over 5-HT₁Asupported
Binding affinities of 21 indolealkylamine derivatives at 5-HT1A, 5-HT2A, 5-HT2B by radioligand competition. 4-hydroxylated derivatives show 25-380-fold selectivity for 5-HT2A vs 5-HT1A. pmid:2139186
The N-methyl-N-ethyl substitution pattern falls within the range associated with preserved high 5-HT₂A affinity; N,N-dialkyl groups larger than N,N-diisopropyl markedly reduce binding at both 5-HT₂A and 5-HT₁A sites.supported
N,N-dialkyl size secondary determinant; groups larger than diisopropyl markedly reduce affinity. pmid:2139186
Zhai et al. identified additional phase I pathways for 4-AcO-DMT including hydroxylation, N-demethylation, and oxidation, with phase II conjugation (glucuronidation) also observedsupported
Phase II: glucuronidation, sulfation. N-demethylation, hydroxylation. dta.3255
Malaca et al. confirmed analogous metabolic transformation for 4-AcO-DiPT in human hepatocyte preparations — hydrolysis to the 4-hydroxy metabolite followed by N-dealkylation, oxidation, glucuronidation, and sulfation. 4-AcO-MET is expected to follow an analogous biotransformation sequence, but this remains unverified.supported
4-AcO-DiPT metabolism in human hepatocytes. Primary metabolite via ester hydrolysis is 4-OH-DiPT. Phase II: glucuronidation and sulfation. N-oxidation and N-dealkylation also occur. metabo12080705
summary6 · 5 ok
Its solid-state crystal structure was confirmed by X-ray diffraction in 2021.supported
Solid-state structures of three psilacetin derivatives including 4-AcO-MET (4-acetoxy-N-ethyl-N-methyl-tryptammonium) hydrofumarate salt. s2056989021000116
The 4-hydroxylated tryptamine class displays 25–380-fold selectivity for 5-HT₂A over 5-HT₁A, and receptor binding panels confirm high 5-HT₂A selectivity for 4-substituted tryptamines including 4-AcO-MET specificallypartially supported
4-hydroxylated derivatives show 25-380-fold selectivity for 5-HT2A vs 5-HT1A. pmid:2139186
The 4-hydroxylated tryptamine class displays 25–380-fold selectivity for 5-HT₂A over 5-HT₁A, and receptor binding panels confirm high 5-HT₂A selectivity for 4-substituted tryptamines including 4-AcO-MET specificallysupported
4-substituted compounds show high selectivity for 5-HT2AR. Includes 4-AcO-MET in binding panel. jpet.122.001454
In silico modelling of the structural analog 4-AcO-DMT predicts an oral LD₅₀ in the 100–500 mg/kg range (Cramer Class III), but this has not been experimentally validatedsupported
In silico toxicology of 6 tryptamines including 4-AcO-DMT. Predicted oral LD50 100-500 mg/kg. Cramer Class III. s00204-026-04365-4
Tolerance develops rapidly via 5-HT₂A receptor downregulation, with single-dose tolerance observable within 24 hours and full reset within approximately 7 dayspartially supported
Single-dose tolerance after 24h. 5-HT2AR downregulation in frontal cortex. acschemneuro.2c00170
Claim in summary — inconclusiveinconclusiveworking →
comparative-pharmacology3 · 1 ok
Glatfelter et al. tested this matrix and established that 4-acetoxy compounds display somewhat weaker binding affinities than the corresponding 4-hydroxy analogs but maintain similar receptor target profiles across serotonin receptor subtypessupported
4-acetoxy analogues show somewhat weaker binding affinities but similar target profiles to 4-hydroxy compounds. acsptsci.2c00222
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
chemistry2 · 2 ok
These identifiers were confirmed via PubChem CID 71308138 and are consistent with the X-ray crystal structure reported by Pham et al.supported
Solid-state structures of three psilacetin derivatives including 4-AcO-MET (4-acetoxy-N-ethyl-N-methyl-tryptammonium) hydrofumarate salt. s2056989021000116
The X-ray crystal structure of 4-AcO-MET hydrofumarate (C₁₅H₂₁N₂O₂⁺·C₄H₃O₄⁻) reveals a protonated tryptammonium cation paired with a fumarate anion, consolidated by N–H···O and O–H···O hydrogen bondssupported
4-AcO-MET (4-acetoxy-N-ethyl-N-methyl-tryptammonium) hydrofumarate salt. Crystal structure consolidation via N-H...O and O-H...O hydrogen bonds. s2056989021000116
clinical-evidence2 · 2 ok
McIntyre et al. reported a fatality in which 4-HO-MET (the active metabolite of 4-AcO-MET) was detected by GC-MS in postmortem toxicologysupported
4-HO-MET (active metabolite of 4-AcO-MET) also detected by GC-MS, not quantified. bkv089
Co-medications included venlafaxine, olanzapine, lorazepam, and hydroxyzine at therapeutic concentrationssupported
Co-medications: venlafaxine, olanzapine, lorazepam, hydroxyzine at therapeutic levels. bkv089
history2 · 2 ok
The solid-state X-ray crystal structure of 4-AcO-MET hydrofumarate was determined by Pham et al. in 2021, confirming the molecular geometry of the protonated tryptammonium cation paired with a fumarate counterion (C₁₅H₂₁N₂O₂⁺·C₄H₃O₄⁻)supported
Solid-state structures of three psilacetin derivatives including 4-AcO-MET (4-acetoxy-N-ethyl-N-methyl-tryptammonium) hydrofumarate salt. Crystal structure consolidation via N-H...O and O-H...O hydrogen bonds. s2056989021000116
In 2021, Ding et al. identified 4-OH-MET (the active metabolite) in seized drug material in China, using GC-QTOF-MS and UPLC-LTQ-Orbitrap MS with NMR confirmationsupported
4-OH-MET identified in white powder from actual drug case by GC-QTOF-MS, UPLC-LTQ-Orbitrap MS and 1H-NMR. j.issn.1004-5619.2021.310305
pharmacokinetic-detail2 · 2 ok
4-AcO-DMT (N,N-dimethyl analog): Zhai et al. characterized in vitro phase I metabolism in pooled human liver microsomes using UHPLC-Q-Orbitrap MS. Ester hydrolysis to psilocin (4-HO-DMT) was the most abundant metabolic pathway. Additional phase I metabolites arose from hydroxylation, N-demethylation, and oxidation. Phase II metabolism included glucuronide conjugation.supported
4-AcO-DMT metabolism in pooled human liver microsomes. 15 metabolites. Primary: hydrolysis to psilocin. Phase II: glucuronidation, sulfation. N-demethylation, hydroxylation. dta.3255
4-AcO-DiPT (N,N-diisopropyl analog): Malaca et al. profiled metabolism in human hepatocyte preparations using LC-HRMS/MS. The predominant pathway was ester hydrolysis to 4-HO-DiPT, followed by N-dealkylation, oxidation, glucuronidation, and sulfation.supported
4-AcO-DiPT metabolism in human hepatocytes. Primary metabolite via ester hydrolysis is 4-OH-DiPT. Phase II: glucuronidation and sulfation. N-oxidation and N-dealkylation also occur. metabo12080705
neuroscience1 · 1 ok
How do the differential non-serotonergic binding profiles across the N,N-dialkyl series translate to differences in neural activation and subjective experience?supported
Receptor binding profiles for tryptamine psychedelics with 4-position (hydroxy, acetoxy, propionoxy) and N,N-dialkyl substitutions. Includes 4-AcO-MET binding data. acsptsci.2c00222