generation run 2026-04-28
24,852 min completedmodel pipeline-v5plan not recordedrun/bfab76b1…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
- no_substance_specific_binding_data
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
20 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | PubMed | 4-acetoxy tryptamine psilocin prodrug serotonin receptor | 1 | 1 | — |
| 2 | ClinicalTrials.gov · absence | 4-AcO-DET ethacetin | 0 | — | — |
| 3 | PubMed | tryptamine psychedelic cross tolerance serotonin 5-HT2A receptor downregulation | 1 | 1 | — |
| 4 | OpenAlex | diethyltryptamine DET psychedelic serotonin receptor | 10 | 4 | — |
| 5 | PubMed · absence | 4-AcO-DET ethacetin diethyltryptamine acetate pharmacology | 0 | — | — |
| 6 | OpenAlex · absence | 4-acetoxy-DET ethacetin tryptamine psychedelic | 0 | — | — |
| 7 | PubMed | substituted tryptamine serotonin 5-HT2A receptor binding affinity psychedelic | 15 | 4 | — |
| 8 | PubChem | 4-AcO-DET | 1 | 1 | Only result; confirms chemical identity data from seed brief. |
| 9 | PubMed | tryptamine serotonin syndrome drug interaction tramadol | 8 | 2 | — |
| 10 | Web | 4-AcO-DET UK legal status scheduling tryptamine | 10 | 3 | — |
| 11 | PubMed | psychedelic tryptamine head twitch drug discrimination rat mouse | 4 | 3 | — |
| 12 | PubMed | psilocybin psilocin pharmacokinetics CYP metabolism human | 1 | 1 | — |
| 13 | Erowid | 4-AcO-DET stability degradation | 1 | 3 | Key stability and market history data. |
| 14 | PsychonautWiki | 4-AcO-DET pharmacology dosage | 1 | — | Cross-reference for dose data. |
| 15 | Wikidoc | 4-AcO-DET history synthesis legal status | 1 | 3 | Primary historical data about 4-AcO-DET first synthesis. |
| 16 | Web/GOV.UK | UK Psychoactive Substances Act 2016 tryptamine | 10 | 2 | — |
| 17 | MAPS/web | Leuner CZ-74 clinical psycholytic therapy | 1 | — | Historical context for CZ-74/4-HO-DET clinical use. |
| 18 | PubChem/Wikidoc/Erowid | 4-AcO-DET chemical identity cross-reference | 3 | — | Verifying all chemical identity data against primary source. |
| 19 | PubMed | novel psychoactive substance tryptamine intoxication emergency department | 1 | 1 | — |
| 20 | OpenAlex | 4-acetoxy tryptamine prodrug psilocin 5-HT2A receptor | 8 | 3 | — |
104 claims by section — every cited sentence, checked against its source
receptor-pharmacology26 · 20 ok
The primary psychedelic mechanism is 5-ht2a receptor agonismsupported
4-substituted compounds show high selectivity for 5-HT2AR. jpet.122.001454
The primary psychedelic mechanism is 5-ht2a receptor agonismsupported
Review of psychedelic mechanisms beyond 5-HT2A including 5-HT1A, 5-HT2C, TrkB receptors. jneurosci.1384-23.2023
Kozell et al. (2023) characterized 21 substituted tryptamines at 5-ht1a, 5-HT₂A, 5-ht2c, and serotonin-transporter using human-receptor-expressing HEK cells. 4-Substituted tryptamines exhibited high selectivity for 5-HT₂A over 5-HT₁A and 5-HT₂C, with affinities spanning a 100-fold range across compounds tested, including 4-acetoxy derivatives.supported
21 substituted tryptamines at 5-HT1A, 5-HT2A, 5-HT2C and SERT. 4-substituted compounds show high selectivity for 5-HT2AR. jpet.122.001454
Glatfelter et al. (2023) determined receptor binding profiles for tryptamines with 4-position substituents (hydroxy, acetoxy, propionoxy) and N,N-dialkyl substitutions including N,N-diethyl — directly relevant to 4-AcO-DETsupported
4-Acetoxy and 4-propionoxy analogues of 4-hydroxy compounds displayed somewhat weaker binding affinities but similar target profiles across 5-HT receptors and other identified targets. acsptsci.2c00222
McKenna et al. (1990) established that 4-hydroxylated indolealkylamines have 25–380-fold selectivity for the 5-HT₂A site over 5-HT₁Asupported
4-hydroxylated derivatives show 25-380-fold selectivity for 5-HT2A vs 5-HT1A. pmid:2139186
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Secondary agonist activity at 5-HT₁A receptors is documented for the 4-substituted tryptamine classsupported
The tryptamine psychedelics target multiple serotonin receptors, including 5-HT1A. acsptsci.2c00222
At high doses, 5-HT₁A activation attenuates the 5-HT₂A-mediated head twitch response and produces hypothermia and hypolocomotion in mice.supported
4-PrO-DMT displayed dose-related psilocybin-like effects in mice: 5-HT2A-mediated HTR (0.3–3 mg/kg s.c.) and 5-HT1A-mediated hypothermia and hypolocomotion (3–30 mg/kg s.c.). acsptsci.2c00222
Some affinity at 5-HT₂C is present for 4-substituted compounds, but lower than at 5-HT₂A.supported
21 substituted tryptamines at 5-HT1A, 5-HT2A, 5-HT2C and SERT. 4-substituted compounds show high selectivity for 5-HT2AR. jpet.122.001454
Rickli et al. (2016) found that tryptamines including 4-OH-dipt — the closest structurally characterized analog to 4-HO-DET — interacted with the serotonin transporter (SERT) similarly to mdmasupported
Mescaline does not interact with serotonin, norepinephrine, or dopamine transporters — in contrast to MDMA and several tryptamines. j.euroneuro.2016.05.001
Serotonergic psychedelics also interact with TrkB neurotrophin receptors, which may contribute to neuroplasticity effectssupported
Review of psychedelic mechanisms beyond 5-HT2A including 5-HT1A, 5-HT2C, TrkB receptors. Neuroplasticity promotion reviewed. jneurosci.1384-23.2023
The primary psychedelic mechanism is 5-ht2a receptor agonismsupported
4-substituted compounds show high selectivity for 5-HT2AR. jpet.122.001454
The primary psychedelic mechanism is 5-ht2a receptor agonismsupported
Review of psychedelic mechanisms beyond 5-HT2A including 5-HT1A, 5-HT2C, TrkB receptors. jneurosci.1384-23.2023
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Glatfelter et al. (2023) determined receptor binding profiles for tryptamines with 4-position substituents (hydroxy, acetoxy, propionoxy) and N,N-dialkyl substitutions including N,N-diethyl — directly relevant to 4-AcO-DETsupported
4-Acetoxy and 4-propionoxy analogues of 4-hydroxy compounds displayed somewhat weaker binding affinities but similar target profiles across 5-HT receptors and other identified targets. acsptsci.2c00222
McKenna et al. (1990) established that 4-hydroxylated indolealkylamines have 25–380-fold selectivity for the 5-HT₂A site over 5-HT₁Asupported
4-hydroxylated derivatives show 25-380-fold selectivity for 5-HT2A vs 5-HT1A. pmid:2139186
Glatfelter et al. (2022) demonstrated in mouse models that 4-acetoxy tryptamines display nanomolar affinity for most human 5-HT receptor subtypes, including 5-HT₂A and 5-HT₁Apartially supported
SAR for psilocybin and analogs. 4-Acetoxy and 4-hydroxy compounds showed similar pharmacological effects. acsptsci.2c00177
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Secondary agonist activity at 5-HT₁A receptors is documented for the 4-substituted tryptamine classsupported
The tryptamine psychedelics target multiple serotonin receptors, including 5-HT1A. 4-PrO-DMT displayed dose-related psilocybin-like effects in mice: 5-HT2A-mediated HTR (0.3–3 mg/kg s.c.) and 5-HT1A-mediated hypothermia and hypolocomotion (3–30 mg/kg s.c.). acsptsci.2c00222
At high doses, 5-HT₁A activation attenuates the 5-HT₂A-mediated head twitch response and produces hypothermia and hypolocomotion in mice.supported
4-PrO-DMT displayed dose-related psilocybin-like effects in mice: 5-HT2A-mediated HTR (0.3–3 mg/kg s.c.) and 5-HT1A-mediated hypothermia and hypolocomotion (3–30 mg/kg s.c.). acsptsci.2c00222
Some affinity at 5-HT₂C is present for 4-substituted compounds, but lower than at 5-HT₂A.supported
21 substituted tryptamines at 5-HT1A, 5-HT2A, 5-HT2C and SERT. 4-substituted compounds show high selectivity for 5-HT2AR. jpet.122.001454
Rickli et al. (2016) found that tryptamines including 4-OH-dipt — the closest structurally characterized analog to 4-HO-DET — interacted with the serotonin transporter (SERT) similarly to mdmasupported
Mescaline does not interact with serotonin, norepinephrine, or dopamine transporters — in contrast to MDMA and several tryptamines. j.euroneuro.2016.05.001
Serotonergic psychedelics also interact with TrkB neurotrophin receptors, which may contribute to neuroplasticity effectssupported
Review of psychedelic mechanisms beyond 5-HT2A including 5-HT1A, 5-HT2C, TrkB receptors. Neuroplasticity promotion reviewed. jneurosci.1384-23.2023
safety24 · 18 ok
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
This absence may reflect limited clinical detection rather than true absence of adverse events: Malaca et al. (2020) noted that tryptamine contribution to drug overdoses 'may be underestimated' because these compounds are not included in standard toxicology screening panels.supported
morbidity considerable and underestimated. ijms21239279
De la Fuente Revenga et al. (2022) demonstrated in mice that rapid tolerance to 5-HT₂A-mediated head twitch response develops after a single dose, involves 5-HT₂A receptor downregulation in the frontal cortex, and produces cross-tolerance between psychedelics (doi and lsd were tested)supported
Tolerance after single dose. Cross-tolerance between DOI and LSD. DOI caused 5-HT2AR downregulation in frontal cortex. acschemneuro.2c00170
Claim in safety — inconclusiveinconclusiveworking →
The active metabolite 4-HO-DET is a 5-HT₂A agonist that may also interact with serotonin-transporter, creating multiple mechanistic pathways for serotonin-syndrome in combination settings.supported
Mescaline does not interact with serotonin, norepinephrine, or dopamine transporters — in contrast to MDMA and several tryptamines. j.euroneuro.2016.05.001
Tramadol poses the most clearly documented danger. tramadol inhibits SERT, and Baldo (2018) identified it as among the opioids most associated with serotonin syndrome in humanssupported
Tramadol inhibits human SERT in HEK293 cells. Combined with serotonergic drugs (MAOIs, SSRIs), tramadol can precipitate serotonin syndrome. s00204-018-2244-6
Tramadol poses the most clearly documented danger. tramadol inhibits SERT, and Baldo (2018) identified it as among the opioids most associated with serotonin syndrome in humanssupported
Tramadol inhibits serotonin reuptake and has opioid effects that compound serotonergic risk. aph.1q748
Tramadol poses the most clearly documented danger. tramadol inhibits SERT, and Baldo (2018) identified it as among the opioids most associated with serotonin syndrome in humanssupported
Tramadol inhibits human SERT in HEK293 cells. Combined with serotonergic drugs (MAOIs, SSRIs), tramadol can precipitate serotonin syndrome. s00204-018-2244-6
Case reports confirm severe and prolonged serotonin toxicity from tramadolsupported
Case report of severe and prolonged serotonin toxicity from tramadol. Pharmacokinetic study confirming mechanism. 15563650.2021.1955912
Claim in safety — inconclusiveinconclusiveworking →
Monoamine oxidase inhibitors (MAOIs) would be expected to dramatically potentiate effects by inhibiting mao-a-mediated metabolic inactivation of the active metabolite 4-HO-DETsupported
Primary metabolism by CYP2D6 and CYP3A4; secondary MAO-A. pharmaceutics17040411
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
This absence may reflect limited clinical detection rather than true absence of adverse events: Malaca et al. (2020) noted that tryptamine contribution to drug overdoses "may be underestimated" because these compounds are not included in standard toxicology screening panels.supported
morbidity considerable and underestimated. ijms21239279
De la Fuente Revenga et al. (2022) demonstrated in mice that rapid tolerance to 5-HT₂A-mediated head twitch response develops after a single dose, involves 5-HT₂A receptor downregulation in the frontal cortex, and produces cross-tolerance between psychedelics (doi and lsd were tested)supported
Tolerance after single dose. Cross-tolerance between DOI and LSD. DOI caused 5-HT2AR downregulation in frontal cortex. acschemneuro.2c00170
Gatch et al. (2011) found low reinforcement and low abuse-liability for related substituted tryptamines in rodent self-administration paradigmspartially supported
DOM used as training drug. DIPT fully substituted at ED50=1.94 mg/kg. Low abuse liability for DOM in rodents. jpet.111.179705
The active metabolite 4-HO-DET is a 5-HT₂A agonist that may also interact with serotonin-transporter, creating multiple mechanistic pathways for serotonin-syndrome in combination settings.supported
Mescaline does not interact with serotonin, norepinephrine, or dopamine transporters — in contrast to MDMA and several tryptamines. j.euroneuro.2016.05.001
Tramadol poses the most clearly documented danger. tramadol inhibits SERT, and Baldo (2018) identified it as among the opioids most associated with serotonin syndrome in humanssupported
Tramadol inhibits human SERT in HEK293 cells. Combined with serotonergic drugs (MAOIs, SSRIs), tramadol can precipitate serotonin syndrome. s00204-018-2244-6
Tramadol poses the most clearly documented danger. tramadol inhibits SERT, and Baldo (2018) identified it as among the opioids most associated with serotonin syndrome in humanssupported
Tramadol inhibits serotonin reuptake and has opioid effects that compound serotonergic risk. aph.1q748
Tramadol poses the most clearly documented danger. tramadol inhibits SERT, and Baldo (2018) identified it as among the opioids most associated with serotonin syndrome in humanssupported
Tramadol inhibits human SERT in HEK293 cells. Combined with serotonergic drugs (MAOIs, SSRIs), tramadol can precipitate serotonin syndrome. s00204-018-2244-6
Case reports confirm severe and prolonged serotonin toxicity from tramadolsupported
Case report of severe and prolonged serotonin toxicity from tramadol. Pharmacokinetic study confirming mechanism. 15563650.2021.1955912
Case reports confirm severe and prolonged serotonin toxicity from tramadolpartially supported
Reviews the pharmacodynamic basis of tramadol-SSRI serotonin syndrome interactions. Tramadol inhibits serotonin reuptake and has opioid effects that compound serotonergic risk. aph.1q748
Monoamine oxidase inhibitors (MAOIs) would be expected to dramatically potentiate effects by inhibiting mao-a-mediated metabolic inactivation of the active metabolite 4-HO-DETsupported
Primary metabolism by CYP2D6 and CYP3A4; secondary MAO-A. pharmaceutics17040411
pharmacology14 · 14 ok
4-AcO-DET is a presumed prodrug that undergoes hydrolysis via serum esterases to yield 4-HO-DET (ethocin/CZ-74), the pharmacologically active speciessupported
Screened 28 novel psilocin prodrugs using 4-position cleavable groups including acetoxy. 4-acetoxy substitution modulates metabolic processing and pharmacokinetic profile. acs.jmedchem.3c01225
Raithatha et al. (2024) demonstrated that 4-acetoxy groups on indole tryptamines function as cleavable prodrug moieties generating the active 4-hydroxy form, but noted that 4-acetoxy compounds show 'somewhat weaker binding affinities but similar target profiles across serotonin receptors' compared to their 4-hydroxy counterparts.partially supported
Novel prodrugs showed reduced pharmacological exposure vs psilocybin while retaining psilocin activity. acs.jmedchem.3c01225
Class-level data establish that 4-substituted tryptamines exhibit nanomolar 5-ht2a affinity with 25–380-fold selectivity over 5-ht1a and greater selectivity over 5-ht2c.partially supported
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
Class-level data establish that 4-substituted tryptamines exhibit nanomolar 5-ht2a affinity with 25–380-fold selectivity over 5-ht1a and greater selectivity over 5-ht2c.supported
21 substituted tryptamines at 5-HT1A, 5-HT2A, 5-HT2C and SERT. 4-substituted compounds show high selectivity for 5-HT2AR. jpet.122.001454
Raithatha et al. (2024) found that 4-acetoxy prodrugs demonstrated 'reduced pharmacological exposure compared with psilocybin,' suggesting slower or less complete activation than phosphate ester prodrugs.supported
Novel prodrugs showed reduced pharmacological exposure vs psilocybin while retaining psilocin activity. acs.jmedchem.3c01225
By analogy to Psilocin (4-HO-dmt), the active metabolite 4-HO-DET is expected to be metabolized primarily by CYP2D6 and CYP3A4 with secondary contribution from monoamine oxidase A (MAO-A)supported
Primary metabolism by CYP2D6 and CYP3A4; secondary MAO-A. pharmaceutics17040411
Meshkat et al. (2025), in a systematic review of psilocybin pharmacokinetics (14 studies, 112 human participants), reported for psilocin: half-life 1.5–4 hours, Tmax 1.8–4 hours oral, bioavailability 52.7 ± 20%, and primary metabolites 4-hydroxyindole-3-acetic acid (4-HIAA) and 4-hydroxytryptopholsupported
Systematic review of 14 psilocybin PK studies (8 lab, 6 clinical; 112 healthy humans). Psilocin Tmax 1.8–4h; bioavailability 52.7±20%. Elimination half-life 1.5–4h. Metabolites: 4-HIAA and 4-hydroxytryptophol. pharmaceutics17040411
4-AcO-DET is a presumed prodrug that undergoes hydrolysis via serum esterases to yield 4-HO-DET (ethocin/CZ-74), the pharmacologically active speciessupported
Screened 28 novel psilocin prodrugs using 4-position cleavable groups including acetoxy. Novel prodrugs showed reduced pharmacological exposure vs psilocybin while retaining psilocin activity. acs.jmedchem.3c01225
Raithatha et al. (2024) demonstrated that 4-acetoxy groups on indole tryptamines function as cleavable prodrug moieties generating the active 4-hydroxy form, but noted that 4-acetoxy compounds show "somewhat weaker binding affinities but similar target profiles across serotonin receptors" compared to their 4-hydroxy counterparts.partially supported
Novel prodrugs showed reduced pharmacological exposure vs psilocybin while retaining psilocin activity. acs.jmedchem.3c01225
Class-level data establish that 4-substituted tryptamines exhibit nanomolar 5-ht2a affinity with 25–380-fold selectivity over 5-ht1a and greater selectivity over 5-ht2c.partially supported
4-hydroxylated derivatives show 25-380-fold selectivity for 5-HT2A vs 5-HT1A. N,N-dialkyl size secondary determinant. pmid:2139186
Class-level data establish that 4-substituted tryptamines exhibit nanomolar 5-ht2a affinity with 25–380-fold selectivity over 5-ht1a and greater selectivity over 5-ht2c.supported
21 substituted tryptamines at 5-HT1A, 5-HT2A, 5-HT2C and SERT. 4-substituted compounds show high selectivity for 5-HT2AR. jpet.122.001454
Raithatha et al. (2024) found that 4-acetoxy prodrugs demonstrated "reduced pharmacological exposure compared with psilocybin," suggesting slower or less complete activation than phosphate ester prodrugs.supported
Novel prodrugs showed reduced pharmacological exposure vs psilocybin while retaining psilocin activity. acs.jmedchem.3c01225
By analogy to Psilocin (4-HO-dmt), the active metabolite 4-HO-DET is expected to be metabolized primarily by CYP2D6 and CYP3A4 with secondary contribution from monoamine oxidase A (MAO-A)supported
Primary metabolism by CYP2D6 and CYP3A4; secondary MAO-A. pharmaceutics17040411
Meshkat et al. (2025), in a systematic review of psilocybin pharmacokinetics (14 studies, 112 human participants), reported for psilocin: half-life 1.5–4 hours, Tmax 1.8–4 hours oral, bioavailability 52.7 ± 20%, and primary metabolites 4-hydroxyindole-3-acetic acid (4-HIAA) and 4-hydroxytryptopholsupported
Systematic review of 14 psilocybin PK studies (8 lab, 6 clinical; 112 healthy humans). Psilocin Tmax 1.8–4h; bioavailability 52.7±20%. Elimination half-life 1.5–4h. Metabolites: 4-HIAA and 4-hydroxytryptophol. pharmaceutics17040411
comparative-pharmacology8 · 6 ok
Glatfelter et al. (2023) tested both N,N-diethyl and N,N-dimethyl 4-substituted tryptamines and found similar target profiles across serotonin receptors, though specific Ki values for 4-AcO-DET were not reported. 4-AcO-DMT has more extensive pharmacological characterization, including demonstrated nanomolar affinity for 5-ht2a and 5-ht1a.supported
4-Acetoxy and 4-propionoxy analogues of 4-hydroxy compounds displayed somewhat weaker binding affinities but similar target profiles across 5-HT receptors and other identified targets. acsptsci.2c00222
Glatfelter et al. (2023) tested both N,N-diethyl and N,N-dimethyl 4-substituted tryptamines and found similar target profiles across serotonin receptors, though specific Ki values for 4-AcO-DET were not reported. 4-AcO-DMT has more extensive pharmacological characterization, including demonstrated nanomolar affinity for 5-ht2a and 5-ht1a.supported
4-Acetoxy and 4-hydroxy compounds showed similar pharmacological effects. Psilacetin (4-AcO-DMT) acts as prodrug for psilocin. acsptsci.2c00177
Raithatha et al. (2024) demonstrated that acetate ester prodrugs showed reduced pharmacological exposure compared with psilocybin, suggesting the phosphate ester is a more efficient delivery mechanism.supported
Novel prodrugs showed reduced pharmacological exposure vs psilocybin while retaining psilocin activity. acs.jmedchem.3c01225
McKenna et al. (1990) established that N,N-dialkyl group size influences 5-HT₂A binding affinitysupported
N,N-dialkyl size secondary determinant; groups larger than diisopropyl markedly reduce affinity. pmid:2139186
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Raithatha et al. (2024) demonstrated that acetate ester prodrugs showed reduced pharmacological exposure compared with psilocybin, suggesting the phosphate ester is a more efficient delivery mechanism.supported
Novel prodrugs showed reduced pharmacological exposure vs psilocybin while retaining psilocin activity. acs.jmedchem.3c01225
McKenna et al. (1990) established that N,N-dialkyl group size influences 5-HT₂A binding affinitysupported
N,N-dialkyl size secondary determinant; groups larger than diisopropyl markedly reduce affinity. pmid:2139186
summary8 · 7 ok
Claim in summary — inconclusiveinconclusiveworking →
As a presumed prodrug, 4-AcO-DET undergoes hydrolysis via serum esterases to yield 4-HO-DET, which acts as a 5-HT₂A receptor agonist — the primary mechanism of tryptamine psychedelicssupported
4-acetoxy substitution modulates metabolic processing and pharmacokinetic profile. Novel prodrugs showed reduced pharmacological exposure vs psilocybin while retaining psilocin activity. acs.jmedchem.3c01225
No binding affinity data specific to 4-AcO-DET have been published; class-level data for 4-substituted tryptamines indicate nanomolar 5-HT₂A affinity with 25–380-fold selectivity over 5-ht1asupported
4-hydroxylated derivatives show 25-380-fold selectivity for 5-HT2A vs 5-HT1A. pmid:2139186
The compound is not considered habit-forming; rapid tolerance develops via 5-HT₂A downregulation in the frontal cortex, with full reset estimated at approximately 7 days — a pharmacological ceiling on compulsive usepartially supported
Tolerance after single dose. DOI caused 5-HT2AR downregulation in frontal cortex. acschemneuro.2c00170
Its active metabolite CZ-74 (4-HO-DET) was employed in European psycholytic therapy during the 1960s under Hanscarl Leuner, but no formal pharmacological characterization of 4-AcO-DET itself has been publishedsupported
Comprehensive review of psycholytic therapy 1949-1970s, led by Hanscarl Leuner in Germany. Used at 30 European clinical centers. Various substances including tryptamines employed in serial lower-dose sessions. fpsyt.2022.1020505
As a presumed prodrug, 4-AcO-DET undergoes hydrolysis via serum esterases to yield 4-HO-DET, which acts as a 5-HT₂A receptor agonist — the primary mechanism of tryptamine psychedelicssupported
Screened 28 novel psilocin prodrugs using 4-position cleavable groups including acetoxy. 4-acetoxy substitution modulates metabolic processing and pharmacokinetic profile. acs.jmedchem.3c01225
No binding affinity data specific to 4-AcO-DET have been published; class-level data for 4-substituted tryptamines indicate nanomolar 5-HT₂A affinity with 25–380-fold selectivity over 5-ht1asupported
4-hydroxylated derivatives show 25-380-fold selectivity for 5-HT2A vs 5-HT1A. pmid:2139186
The compound is not considered habit-forming; rapid tolerance develops via 5-HT₂A downregulation in the frontal cortex, with full reset estimated at approximately 7 days — a pharmacological ceiling on compulsive usepartially supported
Tolerance after single dose. DOI caused 5-HT2AR downregulation in frontal cortex. acschemneuro.2c00170
chemistry6 · 6 ok
This acetoxy moiety renders 4-AcO-DET a structural ester prodrug: hydrolysis cleaves the acetate group to yield 4-ho-det (ethocin/CZ-74), the active 4-hydroxytryptamine.supported
Screened 28 novel psilocin prodrugs using 4-position cleavable groups including acetoxy. 4-acetoxy substitution modulates metabolic processing and pharmacokinetic profile. acs.jmedchem.3c01225
The N,N-diethyl substitution on the terminal amine distinguishes it from 4-AcO-DMT (N,N-dimethyl) and 4-aco-mipt (N-methyl-N-isopropyl), placing it in the middle range of N,N-dialkyl bulk — smaller than N,N-diisopropyl, which retains substantial 5-ht2a affinity, but larger than the dimethyl group found in the psilocin series.supported
N,N-dialkyl size secondary determinant; groups larger than diisopropyl markedly reduce affinity. pmid:2139186
NMR reference spectra for structurally related 4-acetoxy tryptamines from grey-market samples are available, providing analytical reference for forensic and harm-reduction identification.supported
1H NMR spectra of 43 alleged psychedelic tryptamines from grey-market vendors including 4-acetoxy compounds. Provides analytical reference spectra for forensic identification. isomerdesign-5-supp
This acetoxy moiety renders 4-AcO-DET a structural ester prodrug: hydrolysis cleaves the acetate group to yield 4-ho-det (ethocin/CZ-74), the active 4-hydroxytryptamine.supported
Screened 28 novel psilocin prodrugs using 4-position cleavable groups including acetoxy. Novel prodrugs showed reduced pharmacological exposure vs psilocybin while retaining psilocin activity. acs.jmedchem.3c01225
The N,N-diethyl substitution on the terminal amine distinguishes it from 4-AcO-DMT (N,N-dimethyl) and 4-aco-mipt (N-methyl-N-isopropyl), placing it in the middle range of N,N-dialkyl bulk — smaller than N,N-diisopropyl, which retains substantial 5-ht2a affinity, but larger than the dimethyl group found in the psilocin series.supported
N,N-dialkyl size secondary determinant; groups larger than diisopropyl markedly reduce affinity. pmid:2139186
NMR reference spectra for structurally related 4-acetoxy tryptamines from grey-market samples are available, providing analytical reference for forensic and harm-reduction identification.supported
1H NMR spectra of 43 alleged psychedelic tryptamines from grey-market vendors including 4-acetoxy compounds. Provides analytical reference spectra for forensic identification. isomerdesign-5-supp
pharmacokinetic-detail6 · 6 ok
All parameters below are inferred by structural analogy to psilocin (4-HO-dmt), the best-characterized 4-hydroxytryptamine, via the systematic review of Meshkat et al. (2025).supported
Systematic review of 14 psilocybin PK studies (8 lab, 6 clinical; 112 healthy humans). Psilocin Tmax 1.8–4h; Cmax 8.2±2.8 to 871 ng/mL (dose-dependent); bioavailability 52.7±20%. pharmaceutics17040411
Raithatha et al. (2024) found that 4-acetoxy prodrugs showed reduced pharmacological exposure compared to psilocybin (a phosphate ester prodrug), suggesting either slower hydrolysis, incomplete conversion, or different tissue distributionsupported
Novel prodrugs showed reduced pharmacological exposure vs psilocybin while retaining psilocin activity. acs.jmedchem.3c01225
cyp2d6 is the primary metabolic enzyme for psilocinpartially supported
Primary metabolism by CYP2D6 and CYP3A4; secondary MAO-A. pharmaceutics17040411
All parameters below are inferred by structural analogy to psilocin (4-HO-dmt), the best-characterized 4-hydroxytryptamine, via the systematic review of Meshkat et al. (2025).supported
Systematic review of 14 psilocybin PK studies (8 lab, 6 clinical; 112 healthy humans). pharmaceutics17040411
Raithatha et al. (2024) found that 4-acetoxy prodrugs showed reduced pharmacological exposure compared to psilocybin (a phosphate ester prodrug), suggesting either slower hydrolysis, incomplete conversion, or different tissue distributionsupported
Novel prodrugs showed reduced pharmacological exposure vs psilocybin while retaining psilocin activity. acs.jmedchem.3c01225
cyp2d6 is the primary metabolic enzyme for psilocinpartially supported
Primary metabolism by CYP2D6 and CYP3A4; secondary MAO-A. pharmaceutics17040411
history4 · 4 ok
CZ-74 entered human clinical use during the 1960s within the framework of psycholytic therapy — the European paradigm of psychedelic-assisted psychotherapy. Hanscarl Leuner of the University of Göttingen, the leading figure in European psycholytic therapy and head of the European Medical Society for Psycholytic Therapy (ept), employed CZ-74 and CEY-19 across approximately 30 clinical treatment centers in Europesupported
Comprehensive review of psycholytic therapy 1949-1970s, led by Hanscarl Leuner in Germany. Used at 30 European clinical centers. Various substances including tryptamines employed in serial lower-dose sessions. fpsyt.2022.1020505
The broader psycholytic therapy era from which CZ-74 emerged is reviewed by Passie et al. (2022).supported
Comprehensive review of psycholytic therapy 1949-1970s, led by Hanscarl Leuner in Germany. fpsyt.2022.1020505
CZ-74 entered human clinical use during the 1960s within the framework of psycholytic therapy — the European paradigm of psychedelic-assisted psychotherapy. Hanscarl Leuner of the University of Göttingen, the leading figure in European psycholytic therapy and head of the European Medical Society for Psycholytic Therapy (ept), employed CZ-74 and CEY-19 across approximately 30 clinical treatment centers in Europesupported
Comprehensive review of psycholytic therapy 1949-1970s, led by Hanscarl Leuner in Germany. Used at 30 European clinical centers. Various substances including tryptamines employed in serial lower-dose sessions. fpsyt.2022.1020505
The broader psycholytic therapy era from which CZ-74 emerged is reviewed by Passie et al. (2022).supported
Comprehensive review of psycholytic therapy 1949-1970s, led by Hanscarl Leuner in Germany. fpsyt.2022.1020505
neuroscience4 · 3 ok
Cameron et al. (2023) reviewed evidence that serotonergic psychedelics interact with TrkB neurotrophin receptors, promoting structural neuroplasticity via bdnf/mTOR signaling cascadessupported
Review of psychedelic mechanisms beyond 5-HT2A including 5-HT1A, 5-HT2C, TrkB receptors. Neuroplasticity promotion reviewed. jneurosci.1384-23.2023
Claim in neuroscience — inconclusiveinconclusiveworking →
Cameron et al. (2023) reviewed evidence that serotonergic psychedelics interact with TrkB neurotrophin receptors, promoting structural neuroplasticity via bdnf/mTOR signaling cascadessupported
Review of psychedelic mechanisms beyond 5-HT2A including 5-HT1A, 5-HT2C, TrkB receptors. Neuroplasticity promotion reviewed. jneurosci.1384-23.2023
The psychoplastogen hypothesis proposes that psychedelics promote rapid structural neuroplasticity — dendritic arbor growth, spinogenesis, and synaptogenesis — via 5-HT₂A/TrkB/BDNF/mTOR signalingsupported
Review of psychedelic mechanisms beyond 5-HT2A including 5-HT1A, 5-HT2C, TrkB receptors. Neuroplasticity promotion reviewed. jneurosci.1384-23.2023
clinical-evidence2 · 2 ok
The active metabolite CZ-74 was employed in clinical psycholytic therapy during the 1960s by Hanscarl Leuner and colleagues at approximately 30 European treatment centerssupported
Comprehensive review of psycholytic therapy 1949-1970s, led by Hanscarl Leuner in Germany. Used at 30 European clinical centers. Various substances including tryptamines employed in serial lower-dose sessions. fpsyt.2022.1020505
The active metabolite CZ-74 was employed in clinical psycholytic therapy during the 1960s by Hanscarl Leuner and colleagues at approximately 30 European treatment centerssupported
Comprehensive review of psycholytic therapy 1949-1970s, led by Hanscarl Leuner in Germany. Used at 30 European clinical centers. Various substances including tryptamines employed in serial lower-dose sessions. fpsyt.2022.1020505
effects-overview2 · 1 ok
Claim in effects-overview — inconclusiveinconclusiveworking →
No controlled human studies have documented its subjective effects; all characterization derives from clinical reports on its active metabolite CZ-74 (4-ho-det) and community experience reports.supported
Various substances including tryptamines employed in serial lower-dose sessions. fpsyt.2022.1020505