generation run 2026-04-28
58 min completedmodel pipeline-v5plan not recordedrun/e9ef5952…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
- sparse_evidence
- safety_data_unverified
- no_dependence_studies
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 | PubMed | 3-MeO-PCP 4-MeO-PCP dissociative psychoactive substance detection | 7 | 6 | Selected for clinical/forensic data, several discuss both 3- and 4-MeO-PCP together |
| 2 | PubMed | novel psychoactive substances dissociatives PCP ketamine analogs toxicology | 3 | 2 | Critical papers for history and market context |
| 3 | ClinicalTrials.gov · absence | 4-methoxyphencyclidine 4-MeO-PCP | 0 | 0 | Confirms no clinical trial program exists for this compound |
| 4 | OpenAlex | 4-MeO-PCP methoxyphencyclidine dissociative | 42 | 2 | Highest-cited papers on 4-MeO-PCP pharmacology and NPS context |
| 5 | PubMed | phencyclidine PCP history synthesis arylcyclohexylamine discovery | 1 | 1 | Best available review of PCP parent compound history and pharmacology |
| 6 | PubMed | 4-MeO-PCP 4-methoxyphencyclidine pharmacology | 2 | 2 | Only published case reports directly naming 4-MeO-PCP |
| 7 | PubChem | 4-MeO-PCP | 1 | 1 | Primary chemical identity verification for 4-MeO-PCP |
| 8 | PubMed | 3-MeO-PCP metabolism CYP enzyme human liver microsomes | 1 | 1 | Metabolic pathway data for 3-MeO-PCP to infer 4-MeO-PCP metabolism (class-level inference) |
| 9 | PubMed | 4-MeO-PCP OR 4-methoxyphencyclidine metabolism detection urine blood | 6 | 2 | Analytical detection methods relevant to 4-MeO-PCP |
| 10 | WebSearch | EMCDDA 4-methoxyphencyclidine early warning | 10 | 0 | Historical context |
| 11 | WebSearch | 4-MeO-PCP legal status UK USA Canada Australia | 10 | 2 | Legal status and historical data |
| 12 | PubMed | 3-MeO-PCP 4-MeO-PCP EMCDDA scheduling Europe; phencyclidine NMDA sigma receptor dopamine pharmacology; methoxetamine MXE pharmacology NMDA | 10 | 0 | Background context gathered |
| 13 | PubMed | 1-cyclohexyl-x-methoxybenzene novel psychoactive substance pharmacology mouse | 2 | 2 | Only available animal pharmacology data for this compound class |
| 14 | PloS ONE · absence | Roth 2013 Ki binding data for 4-MeO-PCP | 0 | 0 | Attempted direct data extraction - unsuccessful due to PDF format |
| 15 | PubMed | arylcyclohexylamine PCP analog synthesis analytical characterization | 2 | 2 | Analytical chemistry and structure-activity relationship data |
| 16 | WebSearch | 4-MeO-PCP Sweden scheduling hazardous 2014 | 8 | 0 | Swedish regulatory history |
| 17 | PubMed | 4-methoxyphencyclidine methoxydine case report clinical intoxication | 5 | 3 | Clinical toxicology data for closest analog 3-MeO-PCP relevant to 4-MeO-PCP harm reduction and risk assessment |
| 18 | UNODC | — | 1 | 1 | Official international scheduling status |
| 19 | WebSearch | 4-MeO-PCP CAS 91164-58-8 melting point physical properties | 10 | 1 | Physical property data for substance characterization |
| 20 | WebSearch | 4-MeO-PCP Germany Australia schedule 2024 | 10 | 0 | Legal status research |
85 claims by section — every cited sentence, checked against its source
safety30 · 20 ok
Shaw et al. (2024) report that 4-MeO-PCP induced lethal effects in NIH Swiss mice at tested doses, though the specific lethal dose was not stated in the abstractsupported
Lethal effects induced by 3- OR 4-OMe analogs at tested doses. jpet.123.001942
The single published human fatality involved a peripheral blood concentration of 8.2 mg/L in a polysubstance context (co-detected: 4-HO-MET, venlafaxine, olanzapine, lorazepam, hydroxyzine at therapeutic concentrations)supported
Peripheral blood 8.2 mg/L. Co-medications: venlafaxine, olanzapine, lorazepam, hydroxyzine at therapeutic levels. bkv089
Respiratory: Respiratory depression at high doses, potentially requiring intubationsupported
Two 3-MeO-PCP intoxications: coma, respiratory acidosis, anisocoria with mydriatic pupils, hypothermia. j.forsciint.2016.12.028
Claim in safety — inconclusiveinconclusiveworking →
Musculoskeletal: Rhabdomyolysis risk — documented for 3-methyl-PCP and expected for all NMDA antagonists producing excessive muscle activity; secondary acute kidney injury possiblesupported
Rhabdomyolysis and acute kidney injury documented. s13181-026-01122-y
Hepatic accumulation in the fatality case was substantial (liver concentration 120 mg/kg), though hepatotoxicity was not specifically describedsupported
Liver 120 mg/kg. bkv089
4-MeO-PCP shows 1–143% cross-reactivity across five commercial PCP immunoassayssupported
3-MeO-PCP and 4-MeO-PCP showed cross-reactivity (1-143%) in all five PCP immunoassays evaluated. bkz026
Definitive identification requires GC-MS or LC-MS/MS with certified reference standardssupported
Synthesis and full analytical characterization of 3-MeO-, 4-MeO- and 3-Me-PCP and PCPy analogues. GC-MS, LC-MS/MS, IR, NMR data. dta.1468
Definitive identification requires GC-MS or LC-MS/MS with certified reference standardssupported
GC-MS method development and validation for 3-MeO-PCP/4-MeO-PCP. bkx048
The thermal degradation of 4-MeO-PCP HCl salt during GC analysis may confound quantitative GC-MS results.supported
4-MeO-PCP GC analysis showed notable HCl salt degradation due to para-methoxy group resonance. dta.1468
PCP-like drug discrimination in rodents confirms that 4-MeO-PCP produces PCP-like interoceptive states, supporting the inference that psychological risks parallel those of the PCP class:supported
All novel ACXs substituted at least partially for PCP (drug discrimination). Abuse liability and neurocognitive risk established for arylcyclohexylamine class. jpet.123.001942
Acute psychosis: PCP is the prototypical pharmacological model of psychosis. Dissociative-induced psychotic episodes with paranoia, disorganized behaviour, and agitation are well-documented for PCP and 3-MeO-PCP.supported
Review of PCP neuropsychopharmacology; NMDA receptor hypofunction hypothesis. s0893-133x(98)00060-8
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Shaw et al. (2024) directly established that 4-MeO-PCP substitutes for PCP in drug discrimination, confirming PCP-like interoceptive effects and supporting the inference that it shares the abuse liability profile of PCP.supported
All novel ACXs substituted at least partially for PCP (drug discrimination). Abuse liability and neurocognitive risk established for arylcyclohexylamine class. jpet.123.001942
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
All published fatalities in the MeO-PCP analog literature involve polysubstance exposure with at least one CNS depressantsupported
Combined with amphetamine and alcohol. j.jflm.2019.05.011
The 4-MeO-PCP fatality case involved lorazepam at therapeutic concentrations.supported
Co-medications: venlafaxine, olanzapine, lorazepam, hydroxyzine at therapeutic levels. bkv089
SERT affinity of PCP analogs raises concern for serotonin syndrome when combined with SSRIs, SNRIs, or MAOIssupported
Methoxetamine and PCP analogues showed appreciable affinities for serotonin transporter. journal.pone.0059334
No published cases of serotonin syndrome specifically involve 4-MeO-PCP, but the single fatality case involved venlafaxine (SNRI) co-ingestionsupported
Co-medications: venlafaxine, olanzapine, lorazepam, hydroxyzine at therapeutic levels. bkv089
Claim in safety — inconclusiveinconclusiveworking →
Given the inferred metabolism via CYP2B6, CYP2C19, and CYP2D6, inhibitors of these enzymes (e.g., fluoxetine and paroxetine for CYP2D6; omeprazole for CYP2C19) could theoretically elevate parent drug exposure.supported
CYP2B6 responsible for aliphatic hydroxylations; CYP2C19 and CYP2D6 for O-demethylation. 1570159x14666161018151716
Claim in safety — inconclusiveinconclusiveworking →
Concurrent serotonergic medications (SSRIs, SNRIs, MAOIs): SERT affinity raises serotonin syndrome risk; severity unquantifiedsupported
Methoxetamine and PCP analogues showed appreciable affinities for serotonin transporter. journal.pone.0059334
Claim in safety — inconclusiveinconclusiveworking →
Hepatic impairment: Affects CYP-mediated metabolism; elevated parent drug exposure expectedsupported
CYP2B6 responsible for aliphatic hydroxylations; CYP2C19 and CYP2D6 for O-demethylation. 1570159x14666161018151716
Psychotic disorders or family history of psychosis: PCP-class compounds are the prototypical pharmacological model of psychosissupported
Review of PCP neuropsychopharmacology; NMDA receptor hypofunction hypothesis. s0893-133x(98)00060-8
pharmacology10 · 8 ok
4-MeO-PCP acts as a high-affinity ligand at the phencyclidine binding site on the NMDA glutamate receptor, the primary molecular target responsible for the dissociative and anesthetic effects of the arylcyclohexylamine classsupported
3-MeO-PCE confirmed as high affinity ligand at PCP-site on glutamate NMDA receptor. Pharmacological profiles of ketamine and PCP analogues via NIMH PDSP. journal.pone.0059334
The compound was characterized as part of the NIMH Psychoactive Drug Screening Program (PDSP) alongside methoxetamine and the 3-methoxy PCP isomersupported
Pharmacological profiles of ketamine and PCP analogues via NIMH PDSP. journal.pone.0059334
Claim in pharmacology — inconclusiveinconclusiveworking →
Exact Ki values (in nM) for 4-MeO-PCP at the NMDA receptor, sigma receptors, and serotonin transporter were reported by Roth et al. (2013) but could not be extracted from the available abstract.supported
Pharmacological profiles of ketamine and PCP analogues via NIMH PDSP. PCP analogues exhibited high affinities for sigma receptors. journal.pone.0059334
Beyond the NMDA receptor, 4-MeO-PCP exhibits appreciable affinity for sigma receptors and the serotonin transporter (SERT)supported
Methoxetamine and PCP analogues showed appreciable affinities for serotonin transporter; PCP analogues exhibited high affinities for sigma receptors. journal.pone.0059334
Claim in pharmacology — inconclusiveinconclusiveworking →
Dopamine reuptake inhibition is plausible as a class-level inference — PCP inhibits DAT, contributing to its stimulant and psychotomimetic properties — but no published study has specifically quantified DAT affinity for 4-MeO-PCP. The para-isomer of 1-cyclohexyl-methoxybenzene (structurally analogous) was inactive at mu, kappa, and delta opioid receptors in vitro.partially supported
In vitro: 1-cyclohexyl-x-methoxybenzene (ortho, meta, para) inactive at mu/kappa/delta opioid receptors. ijms22147659
In the morpholine-ring analog series (PCMo), the rank order of NMDAR affinity follows: 3-Me > 3-MeO > PCMo > 3,4-MD > 2-MeO > 4-MeO-PCMo (lowest)supported
NMDAR affinity rank: 3-Me > 3-MeO > PCMo > 3,4-MD > 2-MeO > 4-MeO-PCMo. dta.2213
The metabolic fate of the closest characterized analog, 3-meo-pcp, was elucidated in rat urine and pooled human liver microsomes by Michely et al. (2017):supported
Metabolic fate of 3-MeO-PCP and 3-MeO-PCPy elucidated in rat urine and pooled human liver microsomes. 1570159x14666161018151716
Poor metabolizers at CYP2D6 may show elevated parent drug exposure, though clinical confirmation is lacking.supported
CYP2C19 and CYP2D6 for O-demethylation. 1570159x14666161018151716
clinical-evidence9 · 6 ok
Claim in clinical-evidence — inconclusiveinconclusiveworking →
The STRIDA project in Sweden reported analytically confirmed non-fatal intoxications involving 3-MeO-PCP and/or 4-MeO-PCP from mid-2013supported
STRIDA project case series: analytically confirmed non-fatal intoxications associated with 3-MeO-PCP and/or 4-MeO-PCP in Sweden, use noted starting mid-2013. 15563650.2015.1079325
Seven fatalities in Sweden, all involving polysubstance usepartially supported
Non-fatal intoxication and seven deaths in Sweden, March 2014 to June 2016. j.forsciint.2017.02.034
One fatality in the Netherlands where 3-MeO-PCP was sold mislabeled as ant poison, combined with amphetamine and alcoholsupported
First fatal 3-MeO-PCP case in Netherlands. Substance sold as ant poison. Combined with amphetamine and alcohol. j.jflm.2019.05.011
Claim in clinical-evidence — inconclusiveinconclusiveworking →
Coma (Glasgow Coma Scale 3) in two young men, with respiratory acidosis requiring intubation, anisocoria with mydriatic pupils, and hypothermiapartially supported
Two 3-MeO-PCP intoxications: coma, respiratory acidosis, anisocoria with mydriatic pupils, hypothermia. j.forsciint.2016.12.028
Claim in clinical-evidence — inconclusiveinconclusiveworking →
The most recent and pharmacologically comprehensive rodent study directly testing 4-MeO-PCP found:supported
4-MeO-PCP (4-OMe analog of PCP) directly tested: addition of -OMe at 4-position reduces locomotor effectiveness vs parent PCP. jpet.123.001942
Studies of the 1-cyclohexyl-x-methoxybenzene series (including the para/4-MeO isomer) in mice demonstrated:supported
First demonstration that systemic administration of 1-cyclohexyl-x-methoxybenzene compounds markedly inhibit visual response, promote analgesia, and induce core temperature alterations in mice. hup.2560
history7 · 3 ok
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
PCP's mechanism of action — NMDA receptor hypofunction — later became foundational to the glutamate hypothesis of schizophreniasupported
Review of PCP neuropsychopharmacology; NMDA receptor hypofunction hypothesis. s0893-133x(98)00060-8
Claim in history — inconclusiveinconclusiveworking →
4-MeO-PCP holds the distinction of being the first dissociative research chemical sold onlinesupported
4-MeO-PCP identified as the first dissociative research chemical, appearing on the market in 2008. dta.1620
This event pioneered the online dissociative NPS market that subsequently produced at least 12 additional compounds including methoxetamine, 3-meo-pcp, and others.supported
Historical account of non-medical use of over 30 dissociative compounds. dta.1620
summary7 · 7 ok
PCP-like drug discrimination confirms dissociative interoceptive effectssupported
All novel ACXs substituted at least partially for PCP (drug discrimination). jpet.123.001942
4-MeO-PCP was first synthesized in 1965 by Victor Maddox at Parke-Davis and holds the distinction of being the first dissociative research chemical sold online, introduced to the market in late 2008partially supported
4-MeO-PCP identified as the first dissociative research chemical, appearing on the market in 2008. dta.1620
This event pioneered the online dissociative novel psychoactive substance (NPS) market that subsequently produced over a dozen additional compoundssupported
Historical account of non-medical use of over 30 dissociative compounds. dta.1620
The compound acts as a high-affinity ligand at the phencyclidine binding site on the NMDA glutamate receptor, with additional affinity for sigma receptors and the serotonin transportersupported
PCP analogues exhibited high affinities for sigma receptors. Methoxetamine and PCP analogues showed appreciable affinities for serotonin transporter. journal.pone.0059334
Structure-activity data from the morpholine analog series indicate that para-methoxy substitution reduces NMDAR affinity relative to the meta-isomer, and rodent studies confirm reduced locomotor stimulation compared to PCPpartially supported
NMDAR affinity rank: 3-Me > 3-MeO > PCMo > 3,4-MD > 2-MeO > 4-MeO-PCMo. dta.2213
Structure-activity data from the morpholine analog series indicate that para-methoxy substitution reduces NMDAR affinity relative to the meta-isomer, and rodent studies confirm reduced locomotor stimulation compared to PCPpartially supported
Addition of -OMe at 4-position reduces locomotor effectiveness vs parent PCP. jpet.123.001942
One confirmed fatality involved 4-MeO-PCP as the principal cause of death in a polysubstance context (peripheral blood 8.2 mg/L), though this single case does not establish a lethal thresholdsupported
Postmortem toxicology case: 4-MeO-PCP principal cause of death. Peripheral blood 8.2 mg/L. bkv089
neuroscience6 · 6 ok
PCP and ketamine block NMDA receptors on GABAergic interneurons in the prefrontal cortex, paradoxically disinhibiting glutamatergic pyramidal neurons and producing a downstream surge in cortical glutamate releasesupported
Review of PCP neuropsychopharmacology; NMDA receptor hypofunction hypothesis. s0893-133x(98)00060-8
The resulting disruption of normal prefrontal cortical function underlies the cognitive fragmentation, depersonalization, and reality distortion characteristic of dissociative states. 4-MeO-PCP, acting through the same PCP binding site, is expected to produce qualitatively similar cortical disruption.supported
3-MeO-PCE confirmed as high affinity ligand at PCP-site on glutamate NMDA receptor. journal.pone.0059334
PCP increases dopamine release in the nucleus accumbens and prefrontal cortex through both direct DAT inhibition and indirect mechanisms (NMDA blockade on mesocortical GABAergic interneurons, sigma-1 receptor agonism)supported
Review of PCP neuropsychopharmacology; NMDA receptor hypofunction hypothesis. s0893-133x(98)00060-8
Shaw et al. (2024) assessed psychosis-like neurocognitive effects of PCP-class analogs including 4-MeO-PCP in rodents, though specific prepulse inhibition data for 4-MeO-PCP require full paper access.supported
Abuse liability and neurocognitive risk established for arylcyclohexylamine class. jpet.123.001942
PCP's pharmacology provided the primary experimental basis for the glutamate hypothesis of schizophrenia, which posits that NMDA receptor hypofunction — particularly on cortical GABAergic interneurons — produces the positive, negative, and cognitive symptoms of the disorder. 4-MeO-PCP's confirmed PCP-like drug discrimination profile places it squarely within this framework as a pharmacological model of NMDA hypofunction.supported
Review of PCP neuropsychopharmacology; NMDA receptor hypofunction hypothesis. s0893-133x(98)00060-8
PCP's pharmacology provided the primary experimental basis for the glutamate hypothesis of schizophrenia, which posits that NMDA receptor hypofunction — particularly on cortical GABAergic interneurons — produces the positive, negative, and cognitive symptoms of the disorder. 4-MeO-PCP's confirmed PCP-like drug discrimination profile places it squarely within this framework as a pharmacological model of NMDA hypofunction.supported
PCP was first non-natural man-made illicit drug of abuse; led to NMDA receptor hypofunction hypothesis of schizophrenia and discovery of ketamine. acschemneuro.8b00266
receptor-pharmacology6 · 5 ok
Serotonin syndrome has not been reported for 4-MeO-PCP specifically, but the single published fatality involved co-ingestion with venlafaxine (an SNRI).supported
Co-medications: venlafaxine, olanzapine, lorazepam, hydroxyzine at therapeutic levels. bkv089
Roth et al. (2013) confirmed 4-MeO-PCP as a high-affinity ligand for the PCP binding site within the NMDA receptor ion channel using the NIMH PDSP radioligand displacement assaysupported
Pharmacological profiles of ketamine and PCP analogues via NIMH PDSP. journal.pone.0059334
The rank order 3-Me > 3-MeO > parent > 3,4-MD > 2-MeO > 4-MeO indicates that the 4-MeO position is the least favourable for NMDAR binding in this series.supported
NMDAR affinity rank: 3-Me > 3-MeO > PCMo > 3,4-MD > 2-MeO > 4-MeO-PCMo. dta.2213
PCP and its methoxy analogues — including 4-MeO-PCP — exhibit high affinities for sigma receptorssupported
PCP analogues exhibited high affinities for sigma receptors. journal.pone.0059334
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
The para-methoxy isomer of 1-cyclohexyl-methoxybenzene (structurally analogous to 4-MeO-PCP) was inactive at mu, kappa, and delta opioid receptors in vitrosupported
In vitro: 1-cyclohexyl-x-methoxybenzene (ortho, meta, para) inactive at mu/kappa/delta opioid receptors. ijms22147659
comparative-pharmacology5 · 4 ok
The extended duration is pharmacologically plausible given the lipophilic character of the molecule and the CNS accumulation pattern demonstrated in the single fatality case (central:peripheral blood ratio ~1.7), but has not been confirmed by controlled pharmacokinetic studies.supported
Peripheral blood 8.2 mg/L, central blood 14 mg/L. bkv089
Data from the PCMo (morpholine) analog series establish that 3-MeO substitution preserves or enhances NMDAR affinity relative to the parent scaffold, while 4-MeO substitution reduces itsupported
NMDAR affinity rank: 3-Me > 3-MeO > PCMo > 3,4-MD > 2-MeO > 4-MeO-PCMo. dta.2213
In the piperidine (PCP) series, Roth et al. (2013) characterized both isomers as high-affinity NMDA ligands, but the relative rank order (whether 3-MeO-PCP > 4-MeO-PCP holds in the piperidine series as it does in the morpholine series) requires numerical Ki comparison from the full paper.supported
Pharmacological profiles of ketamine and PCP analogues via NIMH PDSP. journal.pone.0059334
Shaw et al. (2024) directly compared 4-MeO-PCP against PCP and other ring-substituted analogs in rodent locomotor and drug-discrimination paradigms:supported
4-MeO-PCP (4-OMe analog of PCP) directly tested: addition of -OMe at 4-position reduces locomotor effectiveness vs parent PCP; all novel ACXs substituted at least partially for PCP (drug discrimination). jpet.123.001942
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
pharmacokinetic-detail3 · 3 ok
The single published fatality case provides the only human tissue distribution data:supported
Peripheral blood 8.2 mg/L, central blood 14 mg/L, liver 120 mg/kg, vitreous 5.1 mg/L, urine 140 mg/L, gastric contents 280 mg. bkv089
Michely et al. (2017) elucidated the metabolic fate of 3-MeO-PCP using rat urine and pooled human liver microsomes (pHLM), identifying the following CYP-mediated pathways:supported
Metabolic fate of 3-MeO-PCP and 3-MeO-PCPy elucidated in rat urine and pooled human liver microsomes. CYP2B6 responsible for aliphatic hydroxylations; CYP2C19 and CYP2D6 for O-demethylation. 1570159x14666161018151716
All entries above are inferred from 3-MeO-PCP analog data and have not been confirmed for 4-MeO-PCP.supported
Metabolic fate of 3-MeO-PCP and 3-MeO-PCPy elucidated in rat urine and pooled human liver microsomes. 1570159x14666161018151716
chemistry2 · 2 ok
Three positional isomers exist — 2-MeO-PCP, 3-MeO-PCP, and 4-MeO-PCP — each with distinct pharmacological profiles and analytically distinguishable by GC-MS retention time and mass spectral fragmentation.supported
Synthesis and full analytical characterization of 3-MeO-, 4-MeO- and 3-Me-PCP and PCPy analogues. GC-MS, LC-MS/MS, IR, NMR data. dta.1468
Three positional isomers exist — 2-MeO-PCP, 3-MeO-PCP, and 4-MeO-PCP — each with distinct pharmacological profiles and analytically distinguishable by GC-MS retention time and mass spectral fragmentation.supported
GC-MS method development and validation for 3-MeO-PCP/4-MeO-PCP. bkx048