generation run 2026-04-26
61 min completedmodel pipeline-v5plan not recordedrun/0a880269…Selection
Verification
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- seen / partial
- working
The model's own caveats
none raised on this run
Reproduce
- inputs
- 22 source keys (listed under Sources)
- plan
- not recorded — template version, prompt hash and git SHA are written from 2026-09 onward
- model
- pipeline-v5
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- 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 | PubChem | 4-HO-DiPT | 1 | 1 | Single exact compound match - confirms all chemical identity data |
| 2 | PubMed | tryptamine psychedelic serotonin 5-HT2A head twitch response receptor pharmacology | 10 | — | — |
| 3 | WebSearch | 4-HO-DiPT legal status United States UK EU Canada Australia scheduling | 10 | 3 | Legal status across jurisdictions |
| 4 | PubMed | Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens | 1 | 1 | Key binding affinity paper specifically including 4-OH-DiPT |
| 5 | PubMed · absence | 4-hydroxy diisopropyltryptamine serotonin receptor binding pharmacology | 0 | — | — |
| 6 | ClinicalTrials.gov · absence | 4-HO-DiPT diisopropyltryptamine | 0 | — | No trials indexed under compound name |
| 7 | OpenAlex | 4-HO-DiPT diisopropyltryptamine psychedelic tryptamine | 24 | 5 | — |
| 8 | WebSearch | 4-HO-DiPT iprocin Shulgin TiHKAL synthesis history first report | 10 | 2 | Historical synthesis origin and market appearance |
| 9 | PubMed | 4-HO-DiPT 4-hydroxy-N,N-diisopropyltryptamine iprocin | 1 | 1 | Only direct PubMed hit for 4-HO-DiPT; primary preclinical characterization paper with PK data |
| 10 | WebSearch | RE104 4-HO-DiPT clinical trial IND FDA Reset Pharma | 10 | 2 | Critical clinical development news |
| 11 | Crossref | DOI: 10.1002/jhet.5570140113 | 1 | 1 | First synthesis paper confirmed by Crossref |
| 12 | PubMed | Investigation structure-activity relationships psilocybin analogues binding affinity | 1 | 1 | Key SAR data with specific potency value for 4-HO-DiPT |
| 13 | PubMed | tramadol serotonin syndrome mechanism SERT inhibition toxicity | 2 | 1 | Mechanistic basis for tramadol interaction warning |
| 14 | Erowid | TiHKAL #17 4-HO-DiPT | 1 | 1 | Primary Shulgin source for historical effects characterization |
| 15 | WebSearch | DEA 2022 scheduling proposal 4-HO-DiPT withdrawal Federal Register | 10 | 1 | Official DEA legal status documents |
| 16 | WebSearch | 4-HO-DiPT Australia Poisons Standard Schedule 9 | 10 | 0 | Inconclusive - flagged as unverifiable for Australia |
| 17 | WebSearch | RE104 4-HO-DiPT clinical trial IND FDA Reunion Neuroscience | 10 | 3 | Critical recent regulatory and clinical development news |
| 18 | PubMed · absence | 4-hydroxy-N-isopropyltryptamine 4-HO-NiPT synthesis structure metabolite tryptamine | 0 | — | Metabolite characterization papers |
| 19 | Psychedelic Science Review | 4-HO-DiPT binding affinity pharmacology | 1 | 1 | Aggregated binding data and metabolite information with original source citations |
51 claims by section — every cited sentence, checked against its source
pharmacology10 · 7 ok
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Kelly et al. (2024) profiled the compound across all 12 human serotonin GPCRs and classified it as a near-full agonist at 5-HT₂A, 5-HT₂B, and 5-HT₂C, with sex-dependent differences in potency observed in mice (females showing greater sensitivity).supported
Profiled 4-OH-DiPT at all 12 human 5-HT GPCRs; near full agonist at 5-HT2A/2B/2C... Sex differences in potency (female > male). s41386-023-01744-8
Unlike lsd and mescaline, 4-HO-DiPT significantly inhibits the serotonin transporter (SERT) and partially inhibits the norepinephrine transporter (NET), giving it a monoamine transporter interaction profile closer to psilocin than to phenethylamine or ergoline psychedelicssupported
interacts with SERT and partially NET, similar to MDMA but unlike LSD j.euroneuro.2016.05.001
Kelly et al. (2024) further demonstrated that 4-HO-DiPT enhances fear extinction in mice via 5-HT₂A-dependent activation of GABAergic interneurons in the basolateral amygdala (BLA), increasing inhibition of principal neuronssupported
Enhanced fear extinction in mice dose-dependently. Activated BLA interneurons via 5-HT2A to enhance GABAergic inhibition. s41386-023-01744-8
In rats receiving subcutaneous RE104, 4-HO-DiPT exhibited a plasma half-life of approximately 40 minutes, with plasma concentration correlating directly with head-twitch response intensitysupported
4-OH-DiPT half-life 40 min after s.c. RE104 in rats... PK experiments in rats showed plasma 4-HO-DiPT correlated with head-twitch intensity. acschemneuro.4c00058
Metabolic pathway data derive primarily from human hepatocyte incubation studies of 4-AcO-DiPT, which undergoes rapid ester hydrolysis to yield 4-HO-DiPT as its primary active metabolitesupported
4-AcO-DiPT metabolism in human hepatocytes. Primary metabolite via ester hydrolysis is 4-OH-DiPT. metabo12080705
Claim in pharmacology — inconclusiveinconclusiveworking →
By structural analogy with the related diisopropyltryptamine 5-MeO-2-Me-DiPT, CYP2D6, CYP2C19, and CYP3A4 are implicated in N-dealkylation and hydroxylation reactions, with CYP1A2 contributing to ring hydroxylationsupported
CYP1A2, CYP2C19, CYP2D6, CYP3A4 involved in hydroxylation; CYP2C19 and CYP2D6 in O-demethylation; CYP2C19, CYP2D6, CYP3A4 in N-dealkylation. dta.2197
CYP2D6 is the key polymorphic enzyme for indolealkylamines as a class, and individuals with CYP2D6 poor-metabolizer phenotypes may experience altered drug exposure.supported
CYP2D6 plays polymorphic role in metabolism. CYP2D6 polymorphism may represent additional risk factor. s12248-008-9028-5
safety8 · 7 ok
Claim in safety — inconclusiveinconclusiveworking →
The most dangerous pharmacological interactions involve additive serotonergic load. 4-HO-DiPT both directly activates 5-HT₂A receptors and inhibits SERT, creating a dual serotonergic mechanism that increases vulnerability to serotonin toxicity when combined with other serotonergic agents.supported
Ki ~120 nM at 5-HT2A; partial agonist at 5-HT2A; interacts with SERT and partially NET j.euroneuro.2016.05.001
Tramadol inhibits SERT and NET, producing additive serotonergic load atop 4-HO-DiPT's own transporter inhibition and receptor agonismsupported
Tramadol inhibits SERT in HEK293 cells. Combined with serotonergic agents leads to additive serotonin toxicity risk. s00204-018-2244-6
Tramadol inhibits SERT and NET, producing additive serotonergic load atop 4-HO-DiPT's own transporter inhibition and receptor agonismsupported
Tramadol works as prodrug metabolized to active compounds inhibiting serotonin and norepinephrine reuptake. Serotonin toxicity may occur with accumulation of serotonin with tramadol. cureus.26000
MAOIs block the enzymatic degradation of serotonin, and their combination with a direct 5-HT agonist and SERT inhibitor creates severe serotonin toxicity risk.supported
DDIs with IAA agents can lead to serotonin toxicity. s12248-008-9028-5
MAOIs block the enzymatic degradation of serotonin, and their combination with a direct 5-HT agonist and SERT inhibitor creates severe serotonin toxicity risk.supported
Covers adverse effects including serotonin toxicity. s00204-020-02693-7
Concurrent MAOI use — severe serotonin toxicity risk by mechanism (direct 5-HT agonism + SERT inhibition + MAO blockade)supported
5-HT2A receptors mediate alterations of perception and cognition induced by serotonergic psychedelics. Covers adverse effects including serotonin toxicity. s00204-020-02693-7
Concurrent tramadol use — dangerous additive serotonergic mechanism confirmedsupported
Combined with serotonergic agents leads to additive serotonin toxicity risk. FDA issued safety communication in 2016 about opioids and serotonin syndrome. s00204-018-2244-6
neuroscience6 · 5 ok
Claim in neuroscience — inconclusiveinconclusiveworking →
The most substance-specific neural finding for 4-HO-DiPT comes from Kelly et al. (2024), who demonstrated that the compound enhances fear extinction through 5-HT₂A-dependent activation of GABAergic interneurons in the basolateral amygdala (BLA)supported
Enhanced fear extinction in mice dose-dependently. Activated BLA interneurons via 5-HT2A to enhance GABAergic inhibition. s41386-023-01744-8
By structural analogy with psilocin, 4-HO-DiPT may bind the TrkB receptor (BDNF receptor) with high affinity, promoting dendritic growth and synaptic plasticity through mechanisms independent of 5-HT₂A activationsupported
LSD and psilocin directly bind TrkB with affinities 1000-fold higher than other antidepressants. Psychedelic antidepressant effects depend on TrkB binding and BDNF signaling, independent of 5-HT2A activation. s41593-023-01316-5
The sustained antidepressant-like effect of RE104 in the forced swim test — persisting 1 week after a single dose — is consistent with a neuroplasticity-dependent mechanism, as the compound's plasma half-life (40 minutes) cannot account for effects persisting days beyond clearance.supported
4-OH-DiPT half-life 40 min after s.c. RE104 in rats... Significant antidepressant effect in forced swim test at 1 week. acschemneuro.4c00058
The psychoplastogen framework posits that psychedelics exert therapeutic effects through rapid induction of structural neuroplasticity (dendritic branching, spinogenesis) rather than through the subjective psychedelic experience itself. 4-HO-DiPT's sustained antidepressant-like effects in rodents (persisting 1 week after a single dose despite a 40-minute half-life) and its potential TrkB binding support a plasticity-mediated mechanismsupported
4-OH-DiPT half-life 40 min after s.c. RE104 in rats. Short duration (2-3h) psychedelic effects. Significant antidepressant effect in forced swim test at 1 week. acschemneuro.4c00058
The psychoplastogen framework posits that psychedelics exert therapeutic effects through rapid induction of structural neuroplasticity (dendritic branching, spinogenesis) rather than through the subjective psychedelic experience itself. 4-HO-DiPT's sustained antidepressant-like effects in rodents (persisting 1 week after a single dose despite a 40-minute half-life) and its potential TrkB binding support a plasticity-mediated mechanismsupported
Psychedelic antidepressant effects depend on TrkB binding and BDNF signaling, independent of 5-HT2A activation. s41593-023-01316-5
receptor-pharmacology6 · 4 ok
The approximately six-fold discrepancy in 5-HT₂A affinity between studies (Ki ≈ 120 nM vs. 728–922 nM) likely reflects methodological differences — distinct radioligands, cell lines, expression systems, and assay conditions across laboratories — rather than a data errorsupported
4-OH-DiPT: Ki ~120 nM at 5-HT2A j.euroneuro.2016.05.001
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
The Rickli et al. (2016) values derive from cloned human receptors with direct comparison to classic hallucinogens; the Glatfelter et al. (2023) values come from a broader receptor profiling study across multiple tryptamine analogs.supported
Investigated interactions of novel psychoactive tryptamines... compared with classic hallucinogens. j.euroneuro.2016.05.001
The Rickli et al. (2016) values derive from cloned human receptors with direct comparison to classic hallucinogens; the Glatfelter et al. (2023) values come from a broader receptor profiling study across multiple tryptamine analogs.supported
Determined receptor binding profiles for tryptamine psychedelics including 4-HO-DiPT across broad range of targets. acsptsci.2c00222
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Functional characterization by Kelly et al. (2024) classified 4-HO-DiPT as a near-full agonist at 5-HT₂A, 5-HT₂B, and 5-HT₂C across all 12 human serotonin GPCRssupported
Profiled 4-OH-DiPT at all 12 human 5-HT GPCRs; near full agonist at 5-HT2A/2B/2C. s41386-023-01744-8
summary6 · 4 ok
Claim in summary — inconclusiveinconclusiveworking →
4-HO-DiPT acts as a serotonin receptor agonist with primary activity at 5-HT₂A (Ki ≈ 120 nM in one assay, 728–922 nM in another), classified as a near-full agonist at 5-HT₂A, 5-HT₂B, and 5-HT₂Cpartially supported
4-OH-DiPT: Ki ~120 nM at 5-HT2A; partial agonist at 5-HT2A j.euroneuro.2016.05.001
Claim in summary — inconclusiveinconclusiveworking →
4-HO-DiPT acts as a serotonin receptor agonist with primary activity at 5-HT₂A (Ki ≈ 120 nM in one assay, 728–922 nM in another), classified as a near-full agonist at 5-HT₂A, 5-HT₂B, and 5-HT₂Csupported
near full agonist at 5-HT2A/2B/2C s41386-023-01744-8
Unlike lsd, it also inhibits SERT and partially inhibits NET, placing its pharmacological profile closer to psilocinsupported
interacts with SERT and partially NET, similar to MDMA but unlike LSD j.euroneuro.2016.05.001
The short duration correlates with a plasma half-life of approximately 40 minutes in rats following prodrug administration.supported
4-OH-DiPT half-life 40 min after s.c. RE104 in rats. Short duration (2-3h) psychedelic effects. acschemneuro.4c00058
comparative-pharmacology5 · 3 ok
In the mouse head-twitch response assay — the standard rodent behavioural proxy for human psychedelic activity — 4-HO-DiPT (ED₅₀ = 3.46 μmol/kg) is approximately 4.3-fold less potent than psilocin (ED₅₀ = 0.81 μmol/kg)supported
4-HO-DiPT ED50=3.46 μmol/kg in mouse head-twitch response, less potent than psilocin (0.81). acsptsci.0c00176
Among the 17 tryptamines evaluated by Klein et al. (2021), 4-HO-DiPT and its acetoxy prodrug 4-AcO-DiPT produced longer-lasting head-twitch responses than other 4-hydroxytryptamines in the same seriessupported
4-HO-DiPT and 4-AcO-DiPT produced longer-lasting effects than other compounds. acsptsci.0c00176
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Rickli et al. (2016) directly compared 4-HO-DiPT to classical hallucinogens and found that, like psilocin, it significantly interacts with SERT — a property not shared by lsd or mescalinesupported
interacts with SERT and partially NET, similar to MDMA but unlike LSD j.euroneuro.2016.05.001
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
history4 · 1 ok
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
The compound entered formal clinical development when Reunion Neuroscience developed luvesilocin (RE104), a glutarate ester prodrug of 4-HO-DiPT designed for subcutaneous administrationsupported
RE104, a glutarate ester prodrug of 4-OH-DiPT. 4-OH-DiPT half-life 40 min after s.c. RE104 in rats. acschemneuro.4c00058
Claim in history — not_supportednot supportedworking →
pharmacokinetic-detail3 · 2 ok
The 40-minute half-life following subcutaneous RE104 administration in rats is consistent with the 2–3 hour total subjective duration observed in human self-reports, assuming approximately 3–4 half-lives to reach sub-threshold plasma concentrationssupported
4-OH-DiPT half-life 40 min after s.c. RE104 in rats. Short duration (2-3h) psychedelic effects. acschemneuro.4c00058
Metabolic data derive from human hepatocyte studies of the prodrug 4-AcO-DiPTsupported
4-AcO-DiPT metabolism in human hepatocytes. metabo12080705
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
chemistry2 · 1 ok
Claim in chemistry — inconclusiveinconclusiveworking →
The compound is the active metabolite of 4-AcO-DiPT (via ester hydrolysis of the 4-position acetoxy group) and the pharmacologically active species released by the clinical prodrug luvesilocin (RE104), a glutarate ester.supported
RE104, a glutarate ester prodrug of 4-OH-DiPT. acschemneuro.4c00058
clinical-evidence1 · 1 ok
Bryson et al. (2024) demonstrated that a single dose of RE104 (1 mg/kg s.c.) significantly reduced immobility in the forced swim test at 1 week versus vehicle (p < 0.001), indicating a sustained antidepressant-like effect outlasting acute drug exposuresupported
Significant antidepressant effect in forced swim test at 1 week. acschemneuro.4c00058