generation run 2026-05-10
897 min failedmodel pipeline-v5plan not recordedrun/50511c7b…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
- sparse_evidence
- structural_inference
- safety_data_unverified
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
- streams
- none — agent transcripts are persisted from 2026-09 onward
22 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | PubMed | PMID 36984871 | 1 | 1 | Primary source confirmed via API |
| 2 | Web | PCE eticyclidine Schedule I DEA controlled substance US federal | 10 | 1 | Establishes parent compound scheduling which informs analog status of 3-HO-PCE |
| 3 | PubMed | PMID 6273187 | 1 | 1 | Foundational paper establishing opioid activity of 3-hydroxy arylcyclohexylamines - directly relevant to 3-HO-PCE's proposed opioid activity |
| 4 | PubMed | 3-HO-PCE hydroxyeticyclidine dissociative | 1 | 1 | Only published primary study directly on 3-HO-PCE; selected as primary source |
| 5 | OpenAlex | 3-HO-PCE hydroxyeticyclidine arylcyclohexylamine opioid NMDA | 1 | 0 | No relevant pharmacology papers found via OpenAlex for this compound specifically |
| 6 | PubMed | 3-MeO-PCE methoxeticyclidine pharmacology case report toxicity | 1 | 1 | Critical safety data — fatal case involving closest published analog 3-MeO-PCE |
| 7 | Web | 3-HO-PCE controlled substance scheduling | 10 | 0 | Legal status established via class-level coverage rather than direct scheduling |
| 8 | PubChem | 3-HO-PCE | 1 | 1 | Verified chemical identity data against brief seed data — formula and MW confirmed |
| 9 | PubMed | arylcyclohexylamine NPS forensic detection analytical | 9 | 6 | Wallach 2016 directly characterizes 3-MeO-PCE; Tang 2018/2020 O-PCE and 2F-DCK cluster cases relevant for class safety profile |
| 10 | ClinicalTrials.gov · absence | 3-HO-PCE hydroxyeticyclidine dissociative | 0 | 0 | No trials exist for this emerging compound |
| 11 | Web | 3-HO-PCE hydroxyeticyclidine history discovery research chemical first appearance | 10 | 2 | PsychonautWiki confirmed dose data; CFSRE monograph is a primary forensic reference |
| 12 | PubMed | PMID 23527166 | 1 | 1 | Directly characterizes closest analog's pharmacology via validated binding assays |
| 13 | PubMed | arylcyclohexylamine designer drug novel psychoactive substance pharmacology | 3 | 3 | Selected Wallach 2018 and 3-methyl-PCP case for class context; methoxphenidine less relevant |
| 14 | PMC WebFetch | — | 1 | 1 | Primary source - key metabolism and detection data |
| 15 | OpenAlex | phencyclidine new psychoactive substances NPS review 2018 2019 2020 | 10 | 3 | High-citation landmark papers for ketamine class pharmacology |
| 16 | Web | 3-HO-PCE SMILES CAS number InChI chemical structure | 10 | 0 | InChIKey discrepancy flagged for editorial review; CAS number also uncertain. PubChem API result preferred. |
| 17 | ClinicalTrials.gov · absence | 3-HO-PCE dissociative hydroxyeticyclidine | 0 | 0 | Confirmed absence of clinical trials |
| 18 | Web | Wallach Brandt phencyclidine-based new psychoactive substances 2019 review | 10 | 4 | Critical sources for 3-HO-PCP pharmacology, toxicity, and history; directly relevant to 3-HO-PCE |
| 19 | PubMed | PMID 32311838 | 1 | 1 | Pharmacokinetic and toxicokinetic data for closest analog; protein binding and blood/brain distribution |
| 20 | PubMed | PMID 31482320 | 1 | 1 | Only published acute clinical toxicity case for closest pharmacological analog (3-HO-PCP) |
| 21 | PubMed | PMID 37279962 | 1 | 1 | Fatal case with highest reported blood concentration; documents synthesis date (1978) and polydrug lethality risk |
| 22 | Cross-reference · absence | 3-HO-PCE vs 3-HO-PCP structural comparison pharmacology | 0 | 0 | Structural analog inference documented as basis for pharmacological class assignment |
70 claims by section — every cited sentence, checked against its source
safety19 · 16 ok
Every published fatality involving 3-HO-PCP or 3-MeO-PCE occurred in a polydrug contextsupported
42-year-old polydrug user. j.forsciint.2021.110852
The Ameline et al. (2023) fatality involved co-ingested methadone.supported
Co-ingested: nordiazepam, methylphenidate, amisulpride, methadone, benzoylecgonine. bkad031
The Gicquel et al. (2021) fatality involved concurrent 2F-DCK use.supported
First fatal case involving 2F-DCK and 3-MeO-PCE. j.forsciint.2021.110852
Dunlop et al. (2020) reported an analytically confirmed case of acute 3-HO-PCP toxicity in a 56-year-old male presenting with hyperthermia (39.9°C), sinus tachycardia (150 bpm), reduced consciousness, ocular clonus, and vertical nystagmussupported
Patient (56-year-old male): hyperthermia (39.9°C), sinus tachycardia (150 bpm), reduced consciousness, ocular clonus, vertical nystagmus. s13181-019-00734-x
Ameline et al. (2023) reported a fatal 3-HO-PCP intoxication: a 38-year-old male found dead with peripheral blood 3-HO-PCP concentration of 524 ng/mL — the highest reported in published literaturesupported
38-year-old male found dead with 3-OH-PCP powder. Blood concentration 524 ng/mL (highest reported). bkad031
Claim in safety — inconclusiveinconclusiveworking →
Davidsen et al. (2020) reported 3-HO-PCP blood concentrations of 0.013 mg/kg in a living user and 0.095 mg/kg in a deceased individualsupported
Blood concentrations: 0.013 mg/kg (living) and 0.095 mg/kg (deceased). dta.2807
From 25 analytically confirmed O-PCE (eticyclidine family) acute poisoning cases, the clinical presentation included impaired consciousness (84%), confusion (60%), abnormal behaviour (44%), hypertension (80%), tachycardia (40%), and convulsion (16%)partially supported
56 cases of O-PCE acute poisoning. Main symptoms: impaired consciousness 84%, confusion 60%, hypertension 80%, tachycardia 40%, convulsion 16%. j.forsciint.2018.07.014
Claim in safety — inconclusiveinconclusiveworking →
The opioid component (naloxone-reversible, as demonstrated for 3-HO-PCP) introduces respiratory depression risk at doses where the NMDA component alone might not compromise respirationsupported
PCP and 3-HO-PCP (PCP-3-OH) cause dose-dependent, naloxone-reversible inhibition of guinea pig ileum electrical stimulation. 0014-2999(81)90097-2
Claim in safety — not_supportednot supportedworking →
NMDA receptor antagonists produce a schizophrenia-like psychosis in humans — characterized by positive symptoms (hallucinations, delusions), negative symptoms (withdrawal, flat affect), and cognitive disorganization — that is dose-dependent and typically self-limiting upon drug clearancesupported
NMDA receptor antagonists (PCP, ketamine, MK-801) cause schizophrenia-like psychosis in humans. pmid:8998274
Dextromethorphan — which shares NMDA antagonism and sigma-1 agonism (without direct opioid agonism) with 3-HO-PCE — has been documented to produce dependence, psychosis, and physical withdrawal, establishing precedent for dependence from compounds with overlapping mechanisms.supported
Case documenting dextromethorphan (DXM) dependence, substance-induced psychosis, and physical withdrawal. DXM/dextroporphan shares sigma-1 and NMDA antagonism with arylcyclohexylamine class. pmid:16318953
Every published fatality involving 3-HO-PCP or 3-MeO-PCE occurred in a polydrug contextsupported
Co-ingested: nordiazepam, methylphenidate, amisulpride, methadone, benzoylecgonine. bkad031
By analogy to ketamine pharmacokinetics:supported
Ketamine metabolized via CYP3A and CYP2B6 to norketamine. Poor oral bioavailability due to first-pass metabolism. s40262-016-0383-6
CYP2B6 inhibitors (ticlopidine, clopidogrel): May significantly increase 3-HO-PCE exposure. A 2.4-fold increase in oral S-ketamine AUC was documented with ticlopidine.supported
CYP2B6 inhibitor ticlopidine increased oral ketamine AUC 2.4-fold. clpt.2011.140
History of psychosis or schizophrenia (absolute): NMDA antagonism replicates and potentially precipitates psychotic episodes.supported
NMDA receptor antagonists (PCP, ketamine, MK-801) cause schizophrenia-like psychosis in humans. pmid:8998274
Cardiovascular disease (relative): Tachycardia and hypertension documented in class-level toxidrome data (tachycardia 40%, hypertension 80% in O-PCE cases).supported
hypertension 80%, tachycardia 40%. j.forsciint.2018.07.014
Seizure disorders (relative): Convulsions documented in 16% of O-PCE acute poisoning cases.supported
convulsion 16%. j.forsciint.2018.07.014
pharmacology15 · 9 ok
All arylcyclohexylamines act as uncompetitive antagonists at the phencyclidine/dizocilpine binding site within the NMDA receptor ion channelsupported
PCP receptor ligands are selective NMDA antagonists. Potencies as NMDA antagonists correlated with PCP receptor binding in vitro. pmid:2854262
The compound 3-MeO-PCE — differing from 3-HO-PCE only in bearing a methoxy rather than hydroxy group at the 3-position — was confirmed as a high-affinity NMDA receptor ligand via NIMH Psychoactive Drug Screening Program binding assayssupported
3-MeO-PCE confirmed as high affinity ligand at PCP-site on NMDA receptor. journal.pone.0059334
Claim in pharmacology — inconclusiveinconclusiveworking →
Autoradiographic distribution of [³H]3-OH-PCP binding in rat brain was consistent with NMDA/PCP ion-channel complex localization rather than sigma site binding.supported
Distribution consistent with [3H]TCP and [3H]MK-801, suggesting 3-OH-PCP binds primarily to NMDA/PCP ion-channel complexes over sigma sites. pmid:7620917
Itzhak et al. demonstrated that 3-HO-PCP produces dose-dependent, naloxone-reversible inhibition of guinea pig ileum electrical stimulation, shows high affinity for [³H]morphine binding sites (unlike PCP), and exhibits opioid antagonist activity in the mouse vas deferens bioassaysupported
PCP and 3-HO-PCP (PCP-3-OH) cause dose-dependent, naloxone-reversible inhibition of guinea pig ileum electrical stimulation. Unlike PCP, 3-HO-PCP shows opioid antagonistic effect in mouse vas deferens. Both displace [3H]SKF-10047 binding; 3-HO-PCP also has high affinity for [3H]morphine receptors. 0014-2999(81)90097-2
The clinical significance of arylcyclohexylamine opioid activity was demonstrated by Williams et al. in a randomized crossover study showing that naltrexone pretreatment blocked ketamine's acute antidepressant effects while preserving its dissociative effects — establishing that opioid system activation is mechanistically required for at least some therapeutic outcomes of this compound class.supported
Naltrexone pretreatment blocked antidepressant but not dissociative effects of ketamine. Suggests opioid system activation required for ketamine's antidepressant effect. appi.ajp.2018.18020138
Claim in pharmacology — inconclusiveinconclusiveworking →
The sigma-1 receptor functions as a ligand-regulated chaperone modulating ion channel activity and neurotransmitter release.supported
Sigma-1 receptor as a ligand-regulated molecular chaperone in the ER. j.pharmthera.2009.07.001
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
By analogy to ketamine — the most pharmacokinetically characterized arylcyclohexylamine — CYP3A4 and CYP2B6 are the primary enzymes involved in N-dealkylationsupported
Ketamine metabolized via CYP3A and CYP2B6 to norketamine. s40262-016-0383-6
Claim in pharmacology — inconclusiveinconclusiveworking →
CYP2B6 inhibitors (e.g., ticlopidine) produced a 2.4-fold increase in oral S-ketamine exposure in a controlled human study, suggesting that analogous interactions may affect 3-HO-PCE pharmacokinetics.supported
CYP2B6 inhibitor ticlopidine increased oral ketamine AUC 2.4-fold. clpt.2011.140
Larabi et al. identified the following targets for forensic detection of 3-HO-PCE exposure:supported
M10 recommended for targeted urine screening; M5 for hair analysis. metabo13030432
pharmacokinetic-detail10 · 8 ok
Larabi et al. (2023) characterized 3-HO-PCE metabolism using human liver microsomes and authentic urine and hair samples from confirmed userssupported
First study of 3-HO-PCE metabolism. M10 recommended for targeted urine screening; M5 for hair analysis. metabo13030432
This is the major Phase I pathway and parallels the primary route of ketamine metabolism (N-demethylation to norketamine).supported
Ketamine metabolized via CYP3A and CYP2B6 to norketamine. s40262-016-0383-6
M5 (m/z 192.11503) proved particularly useful as a hair biomarker for long-term exposure monitoring.supported
M5 for hair analysis. metabo13030432
Three O-glucuronide conjugates were identified, formed by glucuronidation of the phenolic hydroxyl or cyclohexane hydroxyl groups.supported
3 phase II (O-glucuronidation). metabo13030432
CYP2B6 is the primary enzyme for N-dealkylation. Ticlopidine (CYP2B6 inhibitor) produced a 2.4-fold increase in oral S-ketamine AUC in humans.supported
CYP2B6 inhibitor ticlopidine increased oral ketamine AUC 2.4-fold. clpt.2011.140
CYP3A4 contributes to N-dealkylation and hydroxylation. Itraconazole (CYP3A4 inhibitor) did not significantly affect oral S-ketamine exposure, suggesting CYP2B6 dominance.supported
CYP3A inhibitor itraconazole did not increase S-ketamine exposure but reduced norketamine formation. clpt.2011.140
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
Davidsen et al. (2020) characterized pharmacokinetic parameters of 3-HO-PCP, the closest structural analog with published data:supported
Plasma protein binding unbound fraction 0.72±0.09. Blood concentrations: 0.013 mg/kg (living) and 0.095 mg/kg (deceased). dta.2807
The relatively high unbound fraction (0.72) indicates limited plasma protein binding and suggests rapid CNS distribution — consistent with the brain:blood ratio of approximately 1.5 observed in postmortem analysissupported
Plasma protein binding unbound fraction 0.72±0.09... brain 1.5x postmortem blood. dta.2807
Claim in pharmacokinetic-detail — not_supportednot supportedworking →
comparative-pharmacology8 · 7 ok
Safety profile: 3-MeO-PCE contributed to respiratory depression in a fatal polydrug case (blood concentration 90 µg/L). 3-HO-PCE theoretically carries additional respiratory risk from its opioid component.supported
3-MeO-PCE blood: 90 ug/L. Death attributed to respiratory depression, polydrug context. j.forsciint.2021.110852
3-HO-PCP (N-piperidyl) and 3-HO-PCE (N-ethyl) share the 3-hydroxyphenyl moiety that confers opioid receptor activitysupported
3-HO-PCP also has high affinity for [3H]morphine receptors. Mediation of alpha- and mu-receptors in opioid effects discussed. 0014-2999(81)90097-2
NMDA affinity: Both compounds are confirmed (3-MeO-PCE) or expected (3-HO-PCE) high-affinity NMDA antagonists.supported
3-MeO-PCE confirmed as high affinity ligand at PCP-site on NMDA receptor. journal.pone.0059334
Ketamine is the most studied arylcyclohexylamine and serves as the pharmacokinetic reference for the classsupported
Ketamine: A Review of Clinical Pharmacokinetics and Pharmacodynamics in Anesthesia and Pain Therapy. s40262-016-0383-6
Opioid activity: Ketamine has weak or negligible direct opioid receptor binding, though its antidepressant effects are blocked by naltrexone. 3-HO-PCE is predicted to have substantially greater direct opioid agonism.supported
Ketamine produces opioid system activation in addition to NMDA antagonism. Naltrexone pretreatment blocked antidepressant but not dissociative effects of ketamine. appi.ajp.2018.18020138
Metabolism: Both are primarily cleared by N-dealkylation via CYP2B6/CYP3A4, but 3-HO-PCE additionally undergoes O-glucuronidation at the phenolic hydroxyl.supported
Ketamine metabolized via CYP3A and CYP2B6 to norketamine. s40262-016-0383-6
Metabolism: Both are primarily cleared by N-dealkylation via CYP2B6/CYP3A4, but 3-HO-PCE additionally undergoes O-glucuronidation at the phenolic hydroxyl.supported
3 phase II (O-glucuronidation). metabo13030432
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
neuroscience6 · 5 ok
Claim in neuroscience — inconclusiveinconclusiveworking →
Autoradiographic mapping of [³H]3-OH-PCP binding (the closest analog with published neuroanatomical data) showed distribution consistent with NMDA/PCP receptor complex rather than sigma receptor sites, with high density in hippocampus, cortex, and striatum.partially supported
Highest densities in hippocampus, olfactory system, cortices, amygdala, thalamus. Distribution consistent with [3H]TCP and [3H]MK-801, suggesting 3-OH-PCP binds primarily to NMDA/PCP ion-channel complexes over sigma sites. pmid:7620917
The mu-opioid agonism conferred by the 3-hydroxy substitution engages neural pathways distinct from NMDA antagonism:supported
3-HO-PCP also has high affinity for [3H]morphine receptors. Mediation of alpha- and mu-receptors in opioid effects discussed. 0014-2999(81)90097-2
Sigma-1 receptors function as intracellular chaperones at the mitochondria-associated endoplasmic reticulum membrane (MAM), modulating calcium signaling, ion channel activity, and neurotransmitter releasesupported
Sigma-1 receptor as a ligand-regulated molecular chaperone in the ER. j.pharmthera.2009.07.001
NMDA receptor antagonists including phencyclidine and ketamine produce dose-dependent neurotoxicity in adult rat brain (Olney lesions) and a schizophrenia-like psychosis in humanssupported
NMDA receptor antagonists (PCP, ketamine, MK-801) cause schizophrenia-like psychosis in humans and neurotoxicity in adult rat brain. pmid:8998274
This neurotoxicity can be prevented by antipsychotics with clozapine-like pharmacologysupported
Clozapine and related antipsychotics prevent NMDA antagonist neurotoxicity in rats. pmid:8998274
summary5 · 5 ok
The first and only published scientific study directly addressing the compound is a 2023 metabolic characterization by Larabi et al., which noted that "little is known about its pharmacological properties, metabolism, and toxicity"supported
First study of 3-HO-PCE metabolism. metabo13030432
The compound is presumed to act as an uncompetitive NMDA receptor antagonist — the class-defining mechanism of all arylcyclohexylamines — with additional mu-opioid receptor agonism conferred by the 3-hydroxyl phenyl substitution, as demonstrated for the structurally analogous 3-HO-PCPsupported
PCP receptor ligands are selective NMDA antagonists. Potencies as NMDA antagonists correlated with PCP receptor binding in vitro. pmid:2854262
The compound is presumed to act as an uncompetitive NMDA receptor antagonist — the class-defining mechanism of all arylcyclohexylamines — with additional mu-opioid receptor agonism conferred by the 3-hydroxyl phenyl substitution, as demonstrated for the structurally analogous 3-HO-PCPsupported
3-HO-PCP also has high affinity for [3H]morphine receptors. Mediation of alpha- and mu-receptors in opioid effects discussed. 0014-2999(81)90097-2
All published fatalities involving closely related compounds (3-HO-PCP, 3-MeO-PCE) occurred in polydrug contextssupported
Co-ingested: nordiazepam, methylphenidate, amisulpride, methadone, benzoylecgonine. bkad031
All published fatalities involving closely related compounds (3-HO-PCP, 3-MeO-PCE) occurred in polydrug contextssupported
42-year-old polydrug user. 3-MeO-PCE blood: 90 ug/L. Death attributed to respiratory depression, polydrug context. j.forsciint.2021.110852
history3 · 3 ok
The 3-hydroxy structural motif was first explored in 1978 with the synthesis of 3-hydroxyphencyclidine (3-HO-PCP), produced to investigate structure-activity relationships of phencyclidine derivativessupported
Notes 3-OH-PCP synthesized in 1978 for structure-activity relationship study. bkad031
This work yielded the critical finding that a hydroxyl group at the 3-position of the phenyl ring confers mu-opioid receptor activity absent in the parent compound — the pharmacological principle that 3-HO-PCE inherits.supported
Unlike PCP, 3-HO-PCP shows opioid antagonistic effect in mouse vas deferens. 3-HO-PCP also has high affinity for [3H]morphine receptors. 0014-2999(81)90097-2
The first published scientific study directly addressing 3-HO-PCE appeared in 2023, when Larabi et al. characterized its metabolism using human liver microsomes and biological samples from confirmed userssupported
First study of 3-HO-PCE metabolism. M10 recommended for targeted urine screening; M5 for hair analysis. metabo13030432
receptor-pharmacology2 · 2 ok
3-MeO-PCE — the N-ethyl analog that differs from 3-HO-PCE only at the phenyl ring substituent (methoxy vs. hydroxy) — was confirmed as a high-affinity NMDA receptor ligand through the NIMH Psychoactive Drug Screening Programsupported
3-MeO-PCE confirmed as high affinity ligand at PCP-site on NMDA receptor. journal.pone.0059334
PCP itself shows no affinity for [³H]morphine binding sites; 3-HO-PCP shows high affinity and naloxone-reversible functional activity in bioassayssupported
3-HO-PCP also has high affinity for [3H]morphine receptors... Unlike PCP, 3-HO-PCP shows opioid antagonistic effect. 0014-2999(81)90097-2
chemistry1 · 1 ok
This substitution is pharmacologically consequential — it confers mu-opioid receptor affinity not present in the unsubstituted parent.supported
Unlike PCP, 3-HO-PCP shows opioid antagonistic effect in mouse vas deferens. 3-HO-PCP also has high affinity for [3H]morphine receptors. 0014-2999(81)90097-2
clinical-evidence1 · 1 ok
The only published human data are the biological samples (urine and hair) from confirmed 3-HO-PCE users analyzed by Larabi et al. (2023) for metabolic characterizationsupported
First study of 3-HO-PCE metabolism. M10 recommended for targeted urine screening; M5 for hair analysis. metabo13030432