generation run 2026-04-21
54 min completedmodel pipeline-v5plan not recordedrun/b8dea8fb…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
none raised on this run
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
20 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | Erowid TiHKAL | — | — | 1 | Primary source for human pharmacology and synthesis data |
| 2 | ClinicalTrials.gov · absence | 4-HO-MiPT miprocin tryptamine psychedelic | 0 | — | — |
| 3 | PubChem | 4-HO-MiPT | 1 | 1 | Primary chemical identity verification |
| 4 | PubMed | serotonin syndrome tryptamine tramadol interaction serotonergic toxicity | 2 | 2 | Supports tramadol interaction warning |
| 5 | PubMed | psilocin analogs 4-hydroxy tryptamine serotonin receptor agonist | 4 | 4 | Directly relevant to tryptamine pharmacology and SAR |
| 6 | WebSearch | Repke 1981 4-HO-MiPT synthesis Journal Heterocyclic Chemistry | — | — | — |
| 7 | OpenAlex | 4-hydroxy-N-methyl-N-isopropyltryptamine pharmacology | 10 | 5 | — |
| 8 | PubMed · absence | 4-hydroxy-N-methyl-N-isopropyltryptamine synthesis receptor binding | 0 | — | — |
| 9 | PubMed · absence | 4-HO-MiPT miprocin tryptamine psychedelic pharmacology | 0 | — | — |
| 10 | OpenAlex | 4-HO-MiPT miprocin tryptamine psychedelic | 1 | 1 | Only published primary research specifically on 4-HO-MiPT |
| 11 | Erowid Legal | — | — | — | — |
| 12 | PubMed | psilocin analogs 4-hydroxy tryptamine serotonin receptor agonist | 1 | — | — |
| 13 | PubChem/ChemicalBook | 4-HO-MiPT CAS 77872-43-6 SMILES | — | — | — |
| 14 | WebFetch/PatentGoogle | — | — | — | — |
| 15 | WebSearch | Repke Ferguson Bates 1981 Journal Heterocyclic Chemistry psilocin analogs synthesis | — | — | — |
| 16 | WebSearch | 4-HO-MiPT EU Germany Netherlands scheduling EMCDDA | — | — | — |
| 17 | WebSearch | 4-HO-MiPT adverse effects toxicity case report overdose NPS | — | — | — |
| 18 | PubMed | Bergh Grafinger Huestis synthetic tryptamine 4-hydroxy metabolism 2024 | 1 | 1 | — |
| 19 | WebFetch/PsychonautWiki | — | — | — | — |
| 20 | OpenAlex | tryptamine NPS new psychoactive substance 4-hydroxy detection metabolism forensic | 8 | — | — |
57 claims by section — every cited sentence, checked against its source
pharmacology11 · 8 ok
4-HO-MiPT is a serotonergic psychedelic acting primarily as an agonist at the serotonin 5-HT₂A receptorsupported
SAR review for tryptamines, ergolines, phenethylamines; 5-HT2A as principal target. 7854_2017_475
4-HO-MiPT is a serotonergic psychedelic acting primarily as an agonist at the serotonin 5-HT₂A receptorsupported
SAR for psilocybin analogs. 4-acetoxy and 4-hydroxy compounds similar pharmacological effects. Tertiary amines only produce HTR. acsptsci.2c00177
4-HO-MiPT is a serotonergic psychedelic acting primarily as an agonist at the serotonin 5-HT₂A receptorsupported
8 N-methyl-N-isopropyltryptamines with various aromatic oxygen substituents evaluated for hallucinogenic activity in man. 4-HO-MiPT described as most interesting, producing classic hallucinogenic profile. pmid:4009612
Claim in pharmacology — inconclusiveinconclusiveworking →
Current evidence identifies Gq-protein signaling — not β-arrestin2 recruitment — as the downstream pathway responsible for psychedelic activity; Gq efficacy at 5-HT₂A predicts head twitch response (HTR) in rodent assays. 4-HO-MiPT, as a 4-hydroxytryptamine, is expected to function as a Gq-activating 5-HT₂A partial agonist.supported
5-HT2A Gq-signaling (not beta-arrestin2) is the molecular pathway predicting psychedelic potential in mice. Threshold Gq activation required. s41467-023-44016-1
Claim in pharmacology — not_supportednot supportedworking →
Only tertiary amines — including the N-methyl-N-alkyl substitution pattern present in 4-HO-MiPT — produce HTR in rodent models.supported
Tertiary amines only produce HTR. acsptsci.2c00177
5-HT₁A co-agonism is a class feature of 4-hydroxytryptamines, mediating sedative, hyperthermic, and hypolocomotor effects at higher doses and attenuating the 5-HT₂A-mediated HTRsupported
Psilocin acts at 5-HT1A, 5-HT2A, 5-HT2C. HTR is 5-HT2A-mediated; locomotor effects are 5-HT1A-mediated. 0269881110388326
5-HT₁A co-agonism is a class feature of 4-hydroxytryptamines, mediating sedative, hyperthermic, and hypolocomotor effects at higher doses and attenuating the 5-HT₂A-mediated HTRsupported
Binding profiles for psilocybin analogs; 4-HO-MiPT not tested; 5-HT1A also targeted. acsptsci.2c00222
Claim in pharmacology — inconclusiveinconclusiveworking →
Metabolic pathways are inferred from the closely related 4-hydroxy-N-ethyl-N-propyltryptamine (4-OH-EPT), studied in human liver microsomessupported
Metabolic characterization of 4-OH-EPT via human liver microsomes. Major pathways: N-dealkylation, hydroxylation, carbonylation, double bond formation. Postmortem blood case confirmed. dta.3668
receptor-pharmacology10 · 8 ok
Pharmacological screening of substituted tryptamines at serotonin receptor subtypes and the serotonin transporter provides the basis for inferring 4-HO-MiPT's receptor selectivity: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
5-HT₂A receptor: Nanomolar affinity expected (primary psychedelic target). 4-Substituted tryptamines show high selectivity for 5-HT₂A over 5-HT₁A and 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
5-HT₁A receptor: Agonist activity expected at class level, though 4-substituted compounds bind 5-HT₁A less potently than 5-substituted compounds (e.g., 5-MeO-MiPT).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
5-HT₁A receptor: Agonist activity expected at class level, though 4-substituted compounds bind 5-HT₁A less potently than 5-substituted compounds (e.g., 5-MeO-MiPT).supported
Fluorinated psilocin analogs binding at 5-HT2A/2C/1A; role of ring substitution in hallucinogenic activity. pmid:11101361
5-HT₂C receptor: Low to moderate affinity expected. Data from the structurally related 4-HO-DiPT (N,N-diisopropyltryptamine) shows notably weaker 5-HT₂C binding than other N,N-dialkyl psilocin analogs, suggesting that bulkier N-alkyl groups differentially reduce 5-HT₂C affinity.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
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Serotonin transporter (SERT): Some non-ring-substituted tryptamines bind SERT, but this interaction is less consistent among 4-substituted compounds.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
The Glatfelter et al. (2023) binding study examined N,N-dialkyl variations on 4-HO, 4-AcO, and 4-PrO tryptamines but used N-methyl-N-n-propyl (MPT) rather than N-methyl-N-isopropyl (MiPT) substitutionsupported
Binding profiles for psilocybin analogs; 4-HO-MiPT not tested; 5-HT1A also targeted; methyl-propyl (n-propyl) analog was tested. acsptsci.2c00222
Structure-activity data from N-substituted tryptamines demonstrate that increasing N-group molecular size progressively alters receptor selectivity profiles.supported
Amino-terminal modifications to 5-MeO-DMT; all tested tryptamines showed selectivity for 5-HT1AR over 5-HT2AR; N-group size influences SERT affinity; HTR mediated primarily by 5-HT2A with 5-HT1A attenuating effect. s41380-024-02506-8
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
safety10 · 10 ok
No human fatalities attributed to 4-HO-MiPT have been published in the peer-reviewed literature.supported
Review of 1,319 NPS adverse events cases 2017-2020. 4-HO-MiPT not among the 60+ NPS with confirmed adverse events. bkac023
No human fatalities attributed to 4-HO-MiPT have been published in the peer-reviewed literature.supported
215 NPS exposures reported Europe/UK/Japan/USA Jan 2020-Mar 2022. 4-HO-MiPT not among reported cases. biology12020273
The absence of adverse event reports in major novel psychoactive substance (NPS) surveillance reviews — including Mohr et al. (2022), Tittarelli et al. (2015), Malaca et al. (2020), and Lo Faro et al. (2023) — reflects limited use and sparse literature coverage rather than a demonstrated safety profilesupported
Review of 1,319 NPS adverse events cases 2017-2020. Covers synthetic cannabinoids, stimulants, hallucinogens, benzodiazepines, and opioids. 4-HO-MiPT not among the 60+ NPS with confirmed adverse events. bkac023
The absence of adverse event reports in major novel psychoactive substance (NPS) surveillance reviews — including Mohr et al. (2022), Tittarelli et al. (2015), Malaca et al. (2020), and Lo Faro et al. (2023) — reflects limited use and sparse literature coverage rather than a demonstrated safety profilesupported
Review of NPS tryptamines: structure, pharmacology, recreational use, toxicology, analytical methods. 1570159x13666141210222409
The absence of adverse event reports in major novel psychoactive substance (NPS) surveillance reviews — including Mohr et al. (2022), Tittarelli et al. (2015), Malaca et al. (2020), and Lo Faro et al. (2023) — reflects limited use and sparse literature coverage rather than a demonstrated safety profilesupported
Review of tryptamine toxicology; 5-HT2A agonists; 22 analytical methods 2015-2020; morbidity underestimated. ijms21239279
The absence of adverse event reports in major novel psychoactive substance (NPS) surveillance reviews — including Mohr et al. (2022), Tittarelli et al. (2015), Malaca et al. (2020), and Lo Faro et al. (2023) — reflects limited use and sparse literature coverage rather than a demonstrated safety profilesupported
215 NPS exposures reported Europe/UK/Japan/USA Jan 2020-Mar 2022. Synthetic opioids most prevalent. 4-HO-MiPT not among reported cases. biology12020273
Tolerance to 4-HO-MiPT's psychedelic effects develops rapidly through agonist-induced 5-HT₂A receptor downregulation, a mechanism that is β-arrestin-2-independentsupported
Psychedelic tolerance via 5-HT2A receptor downregulation; cross-tolerance between psychedelics; beta-arrestin-2-independent. acschemneuro.2c00170
Cross-tolerance between serotonergic psychedelics occurs through the same receptor-level mechanism — demonstrated for DOI and LSD.supported
Psychedelic tolerance via 5-HT2A receptor downregulation; cross-tolerance between psychedelics; beta-arrestin-2-independent. acschemneuro.2c00170
Tramadol inhibits serotonin reuptake (SERT) and has weak direct serotonergic agonist activity; combined with 4-HO-MiPT's 5-HT₂A agonism, the result is additive or synergistic serotonin accumulationsupported
Tramadol inhibits SERT; mechanisms of serotonin toxicity with opioids. s00204-018-2244-6
Tramadol inhibits serotonin reuptake (SERT) and has weak direct serotonergic agonist activity; combined with 4-HO-MiPT's 5-HT₂A agonism, the result is additive or synergistic serotonin accumulationsupported
Case report of possible serotonin syndrome with tramadol + sertraline combination. pmid:9034418
comparative-pharmacology6 · 3 ok
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
4-HO-DiPT (as RE104) has advanced further in clinical development, with published Phase I human pharmacology data — a resource that may inform future 4-HO-MiPT pharmacokinetic predictions once the structural relationship is formally characterized.supported
First formal human evaluation of RE104, a prodrug of 4-OH-DiPT (4-hydroxy-N,N-diisopropyltryptamine). Safety, PK, PD characterized. jcp.0000000000002047
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Within the broader 4-hydroxytryptamine series, N-alkyl chain length and branching systematically modulate potency, duration, and qualitative charactersupported
Amino-terminal modifications to 5-MeO-DMT; all tested tryptamines showed selectivity for 5-HT1AR over 5-HT2AR; N-group size influences SERT affinity; HTR mediated primarily by 5-HT2A with 5-HT1A attenuating effect. s41380-024-02506-8
Increasing N-group molecular size alters receptor selectivity profiles, generally reducing 5-HT₂C engagement while maintaining 5-HT₂A affinity up to a steric threshold. 4-HO-MiPT's position in this series — more potent than psilocin, qualitatively distinct, with an intermediate steric footprint — exemplifies the pharmacological tunability of the 4-hydroxytryptamine scaffoldsupported
21 substituted tryptamines at 5-HT1A, 5-HT2A, 5-HT2C and SERT. 4-substituted compounds show high selectivity for 5-HT2AR. jpet.122.001454
summary6 · 4 ok
Synthesis of 3-[2-(dialkylamino)ethyl]-, 3-[2-(N-methyl-N-alkylamino)ethyl]-, and 3-[2-(cycloalkylamino)ethyl]indol-4-ols}} and first evaluated for psychedelic activity in humans by Repke, Grotjahn, and Shulgin in 1985, 4-HO-MiPT has received minimal formal pharmacological characterizationsupported
Eight N-methyl-N-isopropyltryptamines with various aromatic oxygen substituents evaluated for hallucinogenic activity in man. 4-HO-MiPT described as most interesting, producing classic hallucinogenic profile. pmid:4009612
Claim in summary — inconclusiveinconclusiveworking →
As a 4-hydroxytryptamine, 4-HO-MiPT is presumed to act primarily through 5-HT₂A receptor agonism via Gq-protein signaling, the pathway identified as the molecular determinant of psychedelic activitysupported
5-HT2A Gq-signaling (not beta-arrestin2) is the molecular pathway predicting psychedelic potential in mice. Threshold Gq activation required. s41467-023-44016-1
Claim in summary — inconclusiveinconclusiveworking →
Tolerance develops rapidly through 5-HT₂A receptor downregulation — a β-arrestin-2-independent mechanism demonstrated for the psychedelic class — with cross-tolerance expected across serotonergic psychedelicssupported
Psychedelic tolerance via 5-HT2A receptor downregulation; cross-tolerance between psychedelics; beta-arrestin-2-independent. acschemneuro.2c00170
Serotonin syndrome is a danger when combined with tramadol, MAOIs, or other serotonergic agentssupported
Tramadol inhibits SERT; mechanisms of serotonin toxicity with opioids. s00204-018-2244-6
chemistry4 · 2 ok
Claim in chemistry — inconclusiveinconclusiveworking →
Claim in chemistry — inconclusiveinconclusiveworking →
The terminal nitrogen is tertiary, bearing both a methyl and an isopropyl substituent — a structural feature that confers hallucinogenic activity in the head twitch response assay, as only tertiary amine tryptamines reliably produce this behavioral proxy.supported
Tertiary amines only produce HTR. acsptsci.2c00177
A stable crystalline fumarate salt — bis(4-hydroxy-N-isopropyl-N-methyltryptammonium) fumarate — has been characterized by single-crystal X-ray diffractionsupported
Crystal structure of 4-HO-MiPT fumarate salt. Tryptammonium and fumarate ions in 1D chains via hydrogen bonds. s2056989020002923
clinical-evidence3 · 3 ok
No human data exist beyond Repke et al.'s uncontrolled evaluation of hallucinogenic activity in 1985 and Shulgin's self-experiment accounts in TiHKAL.supported
Eight N-methyl-N-isopropyltryptamines with various aromatic oxygen substituents evaluated for hallucinogenic activity in man. 4-HO-MiPT described as most interesting, producing classic hallucinogenic profile. pmid:4009612
The 1985 study by Repke, Grotjahn, and Shulgin evaluated eight MiPT analogs for hallucinogenic activity in human subjectssupported
Eight N-methyl-N-isopropyltryptamines with various aromatic oxygen substituents evaluated for hallucinogenic activity in man. pmid:4009612
The compound's closest structural relative with active clinical development is 4-HO-DiPT (as RE104), which has completed a Phase I single ascending dose study with published safety, tolerability, and pharmacokinetic data.supported
First formal human evaluation of RE104, a prodrug of 4-OH-DiPT (4-hydroxy-N,N-diisopropyltryptamine). Safety, PK, PD characterized. jcp.0000000000002047
pharmacokinetic-detail3 · 2 ok
Metabolic pathway predictions are derived from human liver microsome studies of the closely related 4-hydroxy-N-ethyl-N-propyltryptamine (4-OH-EPT):supported
Metabolic characterization of 4-OH-EPT via human liver microsomes. Major pathways: N-dealkylation, hydroxylation, carbonylation, double bond formation. dta.3668
The tramadol interaction flagged as dangerous operates primarily through pharmacodynamic (serotonergic) rather than pharmacokinetic mechanisms, though pharmacokinetic contributions cannot be excluded.supported
Tramadol inhibits SERT; mechanisms of serotonin toxicity with opioids. s00204-018-2244-6
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
history2 · 2 ok
The psychedelic effects of 4-HO-MiPT were first formally evaluated in humans by Repke, Grotjahn, and Shulgin in 1985, in a study published in the Journal of Medicinal Chemistry (Vol. 28, No. 7, pp. 892–896)supported
Eight N-methyl-N-isopropyltryptamines with various aromatic oxygen substituents evaluated for hallucinogenic activity in man. 4-HO-MiPT described as most interesting, producing classic hallucinogenic profile. pmid:4009612
In 2020, Chadeayne, Pham, Golen, and Manke published the first crystal structure of 4-HO-MiPT as its fumarate salt using X-ray crystallography in Acta Crystallographica Section Esupported
Crystal structure of 4-HO-MiPT fumarate salt. Tryptammonium and fumarate ions in 1D chains via hydrogen bonds. s2056989020002923