3-MeO-PCE

Shaw et al. demonstrated that the 3-methoxy analog of PCE induced lethal effects in male NIH Swiss mice during dose-response locomotor testingsupported

3-OMe at 3-position of PCE induced lethal effects in mice. PCE-like ACXs had locomotor effects comparable to amphetamines. jpet.123.001942

Gicquel et al. reported the first published fatal intoxication involving 3-MeO-PCEsupported

First fatal case involving 2F-DCK and 3-MeO-PCE. 42-year-old man found dead. j.forsciint.2021.110852

Claim in safety — inconclusiveinconclusiveworking →

Claim in safety — inconclusiveinconclusiveworking →

Chronic heavy use of ketamine is associated with urothelial toxicity (ketamine cystitis), involving direct urothelial apoptosis via P2Y receptor signaling and mitochondrial calcium dysregulation — a mechanism that is NMDA-receptor-independentsupported

Ketamine causes direct urothelial cytotoxicity via mitochondrial stress pathway independent of NMDA receptors. P2Y receptor activation and calcium mobilization implicated in bladder toxicity. j.ajpath.2015.12.014

This risk is mechanistically grounded: the combination of NMDA antagonism (Ki = 61 nM) and SERT inhibition (Ki = 115 nM) produces both glutamatergic disinhibition and serotonergic potentiation — a dual mechanism expected to amplify psychotomimetic effects beyond those of purely glutamatergic dissociatives.supported

3-MeO-PCE confirmed as high affinity ligand at PCP-site on glutamate NMDA receptor. Methoxetamine and PCP analogues showed appreciable affinities for serotonin transporter. journal.pone.0059334

Substance-induced psychotic disorder has been documented for the close structural analog 3-meo-pcp: a case involving escalating oral doses over two weeks produced persistent psychotic symptoms and cognitive impairment, with ¹⁸F-FDG PET/CT changes demonstrating altered cerebral glucose metabolismsupported

Case report of substance-induced psychosis in 29-year-old man following small oral intakes over two weeks then high dose. Brain FDG PET/CT and neuropsychological assessment performed. Persistent psychotic symptoms and impaired cognitive functioning documented. ph17040452

Claim in safety — inconclusiveinconclusiveworking →

Claim in safety — inconclusiveinconclusiveworking →

3-MeO-PCE fully or partially substituted for PCP in drug discrimination assays in rats, confirming PCP-like reinforcing properties and substantial abuse liabilitysupported

All novel ACXs substituted at least partially for PCP (abuse liability). jpet.123.001942

Claim in safety — inconclusiveinconclusiveworking →

Claim in safety — inconclusiveinconclusiveworking →

Serotonergic drugs (SSRIs, SNRIs, MAOIs): 3-MeO-PCE's SERT inhibition (Ki = 115 nM) creates potential for serotonin syndrome when combined with other serotonergic agentssupported

Methoxetamine and PCP analogues showed appreciable affinities for serotonin transporter. journal.pone.0059334

A fatal case involving N-ethyldeschloroketamine (a closely related arylcyclohexylamine) combined with venlafaxine (SNRI) demonstrates the lethal potential of SERT-inhibiting dissociative–SNRI combinationssupported

Fatal case of 52-year-old man who abused N-ethyldeschloroketamine and venlafaxine. Paper explicitly names 3-MeO-PCE as an abused arylcyclohexylamine. bky063

Claim in safety — inconclusiveinconclusiveworking →

Substance-induced psychotic disorder with persistent cognitive impairment has been documented for the close analog 3-meo-pcp.supported

Persistent psychotic symptoms and impaired cognitive functioning documented. ph17040452

Respiratory insufficiency: Any condition compromising baseline respiratory function increases overdose risk, given the respiratory depressant effects of NMDA antagonists confirmed in the polydrug fatal case.supported

Death attributed primarily to respiratory depression from polydrug use. j.forsciint.2021.110852

Hepatic impairment: Metabolism of 3-MeO-PCE proceeds via hepatic biotransformationsupported

14 metabolites identified in zebrafish and human liver microsomes. dta.3488

Claim in safety — inconclusiveinconclusiveworking →

Concurrent serotonergic medication: The strong SERT inhibition renders combination with SSRIs, SNRIs, or MAOIs contraindicated due to serotonin syndrome risk.supported

Methoxetamine and PCP analogues showed appreciable affinities for serotonin transporter. journal.pone.0059334

Concurrent serotonergic medication: The strong SERT inhibition renders combination with SSRIs, SNRIs, or MAOIs contraindicated due to serotonin syndrome risk.supported

Fatal case of 52-year-old man who abused N-ethyldeschloroketamine and venlafaxine. bky063

3-MeO-PCE is a potent non-competitive antagonist at the NMDA glutamate receptor, binding at the phencyclidine site within the open ion channelsupported

3-MeO-PCE confirmed as high affinity ligand at PCP-site on glutamate NMDA receptor. journal.pone.0059334

The NMDA receptor complex is a heterotetrameric ligand-gated ion channel; antagonists at the PCP site block ion flux in a use-dependent manner — requiring prior channel opening by glutamate and glycine co-agonists before the blocking molecule can access the channel poresupported

Comprehensive review of ketamine pharmacology including NMDA receptor antagonism, metabolites, and mechanisms. pr.117.015198

Claim in pharmacology — inconclusiveinconclusiveworking →

This mechanism produces the characteristic dissociative pharmacology: disrupted sensory processing, analgesia, perceptual distortion, and dose-dependent dissociation of consciousness from somatosensory input.supported

Comprehensive review of ACH compounds including ketamine, PCP and eticyclidine derivatives. Covers pharmacology, epidemiology, chemistry, metabolism, and case reports of intoxication. ijms232415574

This mechanism produces the characteristic dissociative pharmacology: disrupted sensory processing, analgesia, perceptual distortion, and dose-dependent dissociation of consciousness from somatosensory input.supported

Dissociative designer drugs primarily act as NMDA receptor antagonists with similar health risks as ketamine. s00204-020-02693-7

At the NMDA PCP site, 3-MeO-PCE displays a Ki of 61 nM — essentially equipotent with PCP (Ki = 59 nM) and approximately threefold more potent than methoxetamine (Ki = 259 nM) and tenfold more potent than ketamine (Ki = 659 nM).supported

Pharmacological profiles of ketamine and PCP analogues via NIMH PDSP. 3-MeO-PCE confirmed as high affinity ligand at PCP-site on glutamate NMDA receptor. journal.pone.0059334

Beyond NMDA antagonism, 3-MeO-PCE inhibits the serotonin transporter (SERT) with a Ki of 115 nM — the strongest SERT affinity among arylcyclohexylamines characterized in the same NIMH-PDSP assay panel, exceeding 3-meo-pcp (Ki = 216 nM), methoxetamine (Ki = 481 nM), and PCP (Ki = 2234 nM)supported

Methoxetamine and PCP analogues showed appreciable affinities for serotonin transporter. journal.pone.0059334

The compound also shows moderate sigma-2 receptor affinity (Ki = 525 nM) but negligible sigma-1 activity (Ki = 4519 nM), contrasting sharply with 3-meo-pcp, which has potent sigma-1 affinity (Ki = 42 nM)supported

PCP analogues exhibited high affinities for sigma receptors. journal.pone.0059334

The dual NMDA antagonism and SERT inhibition is the likely mechanistic basis for the elevated mania and psychosis risk reported for 3-MeO-PCE relative to other dissociatives: serotonergic potentiation layered onto glutamatergic disinhibition produces a stimulant-adjacent pharmacological signature absent from ketamine or dextromethorphan.supported

3-MeO-PCE confirmed as high affinity ligand at PCP-site on glutamate NMDA receptor. Methoxetamine and PCP analogues showed appreciable affinities for serotonin transporter. journal.pone.0059334

The only direct metabolic study employed human liver microsomes (HLM), a zebrafish model, and two human urine samples from forensic casessupported

14 metabolites identified in zebrafish and human liver microsomes... 3-MeO-PCE and metabolites M2, M3, M6 detected in human urine forensic cases. dta.3488

The recommended forensic biomarker is M2 (hydroxylation product), detected in both human urine samples alongside parent 3-MeO-PCE, M3, and M6.supported

M2 (hydroxylation product) recommended as biomarker. 3-MeO-PCE and metabolites M2, M3, M6 detected in human urine forensic cases. dta.3488

By structural analogy with ketamine, where CYP3A4 catalyzes N-demethylation and CYP2B6 contributes to secondary pathways, CYP3A4 and CYP2B6 are the expected primary metabolizing enzymes for 3-MeO-PCEsupported

Metabolism via CYP3A and CYP2B6 to norketamine. s40262-016-0383-6

By structural analogy with ketamine, where CYP3A4 catalyzes N-demethylation and CYP2B6 contributes to secondary pathways, CYP3A4 and CYP2B6 are the expected primary metabolizing enzymes for 3-MeO-PCEsupported

Comprehensive review of ACH compounds including ketamine, PCP and eticyclidine derivatives. Covers pharmacology, epidemiology, chemistry, metabolism, and case reports of intoxication. ijms232415574

The dominance of N-dealkylation and hydroxylation as Phase I pathways is consistent with metabolic patterns observed for methoxetaminesupported

MXE and metabolites (O-desmethyl, N-desethyl, hydroxy, glucuronides, sulfates) detected in postmortem cadaver. bkad084

The dominance of N-dealkylation and hydroxylation as Phase I pathways is consistent with metabolic patterns observed for methoxetaminesupported

Metabolic pathways: hydroxylation, O-demethylation, N-dealkylation, dehydrogenation, combination, glucuronidation/sulfation. dta.3488

Claim in neuroscience — inconclusiveinconclusiveworking →

NMDA receptor blockade on fast-spiking GABAergic interneurons in prefrontal cortex disinhibits pyramidal neuron firing, producing a paradoxical increase in cortical glutamate release — the glutamate surge hypothesis that underlies both the psychotomimetic and potentially neurotoxic effects of PCP-class compoundssupported

Comprehensive review of ketamine pharmacology including NMDA receptor antagonism, metabolites, and mechanisms. pr.117.015198

This mechanism disrupts cortical-subcortical connectivity and produces the characteristic dissociative phenomenology: sensory disconnection, depersonalization, and altered time perception.supported

Comprehensive review of ACH compounds including ketamine, PCP and eticyclidine derivatives. Covers pharmacology, epidemiology, chemistry, metabolism, and case reports of intoxication. ijms232415574

This mechanism disrupts cortical-subcortical connectivity and produces the characteristic dissociative phenomenology: sensory disconnection, depersonalization, and altered time perception.supported

Dissociative designer drugs primarily act as NMDA receptor antagonists with similar health risks as ketamine. s00204-020-02693-7

The concurrent SERT inhibition (Ki = 115 nM) elevates synaptic serotonin concentrations, which may compound cortical excitatory effects via 5-HT₂A receptor activation on layer V pyramidal neurons — a mechanism shared with serotonergic psychedelicssupported

Methoxetamine and PCP analogues showed appreciable affinities for serotonin transporter. journal.pone.0059334

Substance-induced psychotic disorder has been documented for the close analog 3-meo-pcp: Pepe et al. reported persistent psychotic symptoms and cognitive impairment following escalating oral doses over two weeks, with ¹⁸F-FDG PET/CT revealing altered cerebral glucose metabolismsupported

Case report of substance-induced psychosis in 29-year-old man following small oral intakes over two weeks then high dose. Brain FDG PET/CT and neuropsychological assessment performed. Persistent psychotic symptoms and impaired cognitive functioning documented. ph17040452

Claim in neuroscience — inconclusiveinconclusiveworking →

ketamine's antidepressant mechanism involves NMDA blockade triggering a compensatory AMPA receptor–mediated signal cascade (BDNF release, TrkB activation, mTOR-dependent synaptogenesis), producing rapid dendritic spine growth in prefrontal cortexsupported

Comprehensive review of ketamine pharmacology including NMDA receptor antagonism, metabolites, and mechanisms. 1234 citations. pr.117.015198

This model accounts for the dissociative state as a functional disconnection syndrome: sensory input reaches primary cortex but is not integrated with higher-order associative processing.supported

Comprehensive review of ACH compounds including ketamine, PCP and eticyclidine derivatives. Covers pharmacology, epidemiology, chemistry, metabolism, and case reports of intoxication. ijms232415574

Claim in neuroscience — inconclusiveinconclusiveworking →

3-Methoxyeticyclidine (3-MeO-PCE) is a synthetic arylcyclohexylamine dissociative that occupies the high-potency end of its structural class, with NMDA receptor affinity (Ki = 61 nM) approximately equivalent to phencyclidinesupported

3-MeO-PCE confirmed as high affinity ligand at PCP-site on glutamate NMDA receptor. journal.pone.0059334

Claim in summary — inconclusiveinconclusiveworking →

Pharmacological profiling via the NIMH Psychoactive Drug Screening Program followed in 2013, and the first peer-reviewed synthesis and analytical characterization was published in 2016supported

Synthesis of 15 N-alkyl-arylcyclohexylamines including 3-MeO-PCE and 3-MeO-PCPr. Analytical characterizations via GC-MS, HPLC-MS, NMR, UV, IR. dta.1861

3-MeO-PCE blocks ion flux through the NMDA receptor channel at the PCP binding site (Ki = 61 nM), producing use-dependent inhibition of glutamatergic transmissionsupported

3-MeO-PCE confirmed as high affinity ligand at PCP-site on glutamate NMDA receptor. journal.pone.0059334

It additionally inhibits the serotonin transporter (SERT Ki = 115 nM) — the strongest SERT affinity among arylcyclohexylamines profiled in the same assay — while showing negligible sigma-1 receptor activity (Ki = 4519 nM).supported

Methoxetamine and PCP analogues showed appreciable affinities for serotonin transporter; PCP analogues exhibited high affinities for sigma receptors. journal.pone.0059334

3-MeO-PCE induced lethal effects in mice at tested doses, with the 3-methoxy substitution conferring increased acute toxicity over parent eticyclidinesupported

3-OMe at 3-position of PCE induced lethal effects in mice. jpet.123.001942

One polydrug human fatality has been reportedsupported

First fatal case involving 2F-DCK and 3-MeO-PCE. 42-year-old man found dead. j.forsciint.2021.110852

The compound substitutes for PCP in drug discrimination assays, confirming abuse liabilitysupported

All novel ACXs substituted at least partially for PCP (abuse liability). jpet.123.001942

The only published human biological concentration data derive from a single polydrug fatality:supported

Blood concentrations of 3-MeO-PCE: 90 µg/L (peripheral blood), 66 µg/L (vitreous humour), 6.3 mg/L (urine), 3.5 mg/L (bile). j.forsciint.2021.110852

Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →

By structural analogy with ketamine — where CYP3A4 catalyzes N-demethylation to norketamine and CYP2B6 contributes to secondary metabolic pathways — CYP3A4 and CYP2B6 are the expected primary enzymessupported

Metabolism via CYP3A and CYP2B6 to norketamine. s40262-016-0383-6

Xu et al. conducted the only published metabolic study of 3-MeO-PCE, using three complementary systems: human liver microsomes (HLM), zebrafish larvae, and two human urine samples obtained from forensic casessupported

14 metabolites identified in zebrafish and human liver microsomes... 3-MeO-PCE and metabolites M2, M3, M6 detected in human urine forensic cases. dta.3488

The recommended forensic detection biomarker is M2 (hydroxylation product), detected alongside parent compound, M3, and M6 in both human urine samples.supported

M2 (hydroxylation product) recommended as biomarker. 3-MeO-PCE and metabolites M2, M3, M6 detected in human urine forensic cases. dta.3488

By structural analogy with ketamine — where CYP3A4 catalyzes N-demethylation to norketamine and CYP2B6 contributes to secondary metabolic pathways — CYP3A4 and CYP2B6 are the expected primary enzymessupported

Comprehensive review of ACH compounds including ketamine, PCP and eticyclidine derivatives. Covers pharmacology, epidemiology, chemistry, metabolism, and case reports of intoxication. ijms232415574

The metabolic pattern observed (N-dealkylation and hydroxylation as dominant Phase I routes) is consistent with CYP3A4/2B6-mediated biotransformation observed for methoxetamine and other arylcyclohexylaminessupported

MXE and metabolites (O-desmethyl, N-desethyl, hydroxy, glucuronides, sulfates) detected in postmortem cadaver. bkad084

2021: The first published fatal case involving 3-MeO-PCE — a polydrug fatality in France also involving 2F-DCK and 5-meo-dmt — was reported by Gicquel et al.supported

First fatal case involving 2F-DCK and 3-MeO-PCE. 42-year-old man found dead. j.forsciint.2021.110852

Shaw et al. demonstrated lethal effects in mice and PCP-like abuse liability in drug discrimination assays.supported

3-OMe at 3-position of PCE induced lethal effects in mice. All novel ACXs substituted at least partially for PCP (abuse liability). jpet.123.001942

2013: The compound's pharmacological profile was first characterized when Roth and colleagues at the NIMH Psychoactive Drug Screening Program reported binding affinities at NMDA, sigma, and monoamine transporter targets.supported

Pharmacological profiles of ketamine and PCP analogues via NIMH PDSP. 3-MeO-PCE confirmed as high affinity ligand at PCP-site on glutamate NMDA receptor. Methoxetamine and PCP analogues showed appreciable affinities for serotonin transporter; PCP analogues exhibited high affinities for sigma receptors. journal.pone.0059334

2016: Wallach et al. published the first full peer-reviewed synthesis alongside analytical characterization (GC-MS, HPLC-MS, NMR, UV, IR) of 3-MeO-PCE and 14 related N-alkyl-arylcyclohexylamines, establishing definitive reference spectra for forensic identification.supported

Synthesis of 15 N-alkyl-arylcyclohexylamines including 3-MeO-PCE and 3-MeO-PCPr. Analytical characterizations via GC-MS, HPLC-MS, NMR, UV, IR. Positional isomers of aryl methoxyl-substituted compounds were readily distinguishable. dta.1861

2024: Xu et al. published the only direct metabolic study of the compound, identifying 14 metabolites via LC-HRMS in human liver microsomes, zebrafish, and two human forensic urine samplessupported

14 metabolites identified in zebrafish and human liver microsomes... 3-MeO-PCE and metabolites M2, M3, M6 detected in human urine forensic cases. dta.3488

2025: Song et al. included 3-MeO-PCE in a GC-HRMS screening method covering 30 PCP analogs for forensic biological matrices.supported

GC-HRMS screening method for 30 phencyclidine analogs including 3-MeO-PCE in human blood and urine. j.jchromb.2025.124464

All values from Roth et al. 2013 NIMH-PDSP radioligand binding assayssupported

Pharmacological profiles of ketamine and PCP analogues via NIMH PDSP. journal.pone.0059334

SERT affinity. 3-MeO-PCE has the strongest serotonin transporter inhibition (Ki = 115 nM) of any arylcyclohexylamine in the Roth et al. profiling panelsupported

Methoxetamine and PCP analogues showed appreciable affinities for serotonin transporter. journal.pone.0059334

Sigma-1 absence. Unlike 3-meo-pcp (sigma-1 Ki = 42 nM), 3-MeO-PCE has negligible sigma-1 affinity (Ki = 4519 nM)supported

PCP analogues exhibited high affinities for sigma receptors. journal.pone.0059334

NMDA potency. 3-MeO-PCE (Ki = 61 nM) is approximately equipotent with PCP (Ki = 59 nM), threefold more potent than methoxetamine (Ki = 259 nM), and tenfold more potent than ketamine (Ki = 659 nM) at the NMDA PCP site.supported

Pharmacological profiles of ketamine and PCP analogues via NIMH PDSP. 3-MeO-PCE confirmed as high affinity ligand at PCP-site on glutamate NMDA receptor. journal.pone.0059334

The following binding affinities were determined by the NIMH Psychoactive Drug Screening Program using radioligand displacement assays:supported

Pharmacological profiles of ketamine and PCP analogues via NIMH PDSP. journal.pone.0059334

This distinguishes it from ketamine (NMDA Ki = 659 nM, negligible SERT affinity), which acts as a relatively selective NMDA antagonist, and from 3-meo-pcp (NMDA Ki = 20 nM, sigma-1 Ki = 42 nM), whose secondary pharmacology is dominated by sigma-1 agonism rather than serotonergic reuptake inhibition.supported

Pharmacological profiles of ketamine and PCP analogues via NIMH PDSP. 3-MeO-PCE confirmed as high affinity ligand at PCP-site on glutamate NMDA receptor. PCP analogues exhibited high affinities for sigma receptors. journal.pone.0059334

This classification appears to have been conflated with 3-meo-pcp, which has genuine sigma-1 potency (Ki = 42 nM).supported

PCP analogues exhibited high affinities for sigma receptors. journal.pone.0059334

Xu et al. state that 3-MeO-PCE "has a higher N-methyl-D-aspartate receptor binding affinity than phencyclidine"supported

3-MeO-PCE has higher NMDA receptor binding affinity than PCP. dta.3488

The entirety of human clinical data consists of one polydrug fatality report and two forensic urine samples used in metabolite identification.supported

First fatal case involving 2F-DCK and 3-MeO-PCE. 42-year-old man found dead. j.forsciint.2021.110852

The entirety of human clinical data consists of one polydrug fatality report and two forensic urine samples used in metabolite identification.supported

3-MeO-PCE and metabolites M2, M3, M6 detected in human urine forensic cases. dta.3488

Unlike ketamine, which has an established evidence base as a rapid-acting antidepressant, and methoxetamine, for which antidepressant hypotheses have been proposed, no therapeutic rationale has been advanced for 3-MeO-PCEsupported

Methoxetamine pharmacodynamics review. Acts as NMDA receptor antagonist, dopamine reuptake inhibitor, agonist at D2, 5-HT2, muscarinic, sigma-1, mu and kappa opioid receptors. j.mehy.2012.07.002

The parent scaffold consists of a cyclohexane ring bearing both an aryl substituent and an amine nitrogen. 3-MeO-PCE is the 3-methoxy analog of eticyclidine (PCE, N-ethyl-1-phenylcyclohexan-1-amine): the phenyl ring carries a methoxy group at the meta position, and the nitrogen bears an ethyl group rather than the piperidine ring found in phencyclidine or the methyl group found in ketamine.supported

Synthesis of 15 N-alkyl-arylcyclohexylamines including 3-MeO-PCE and 3-MeO-PCPr. Analytical characterizations via GC-MS, HPLC-MS, NMR, UV, IR. dta.1861

The molecular structure comprises a cyclohexane ring with a quaternary carbon (C1) bearing the 3-methoxyphenyl group, an N-ethylamino group, and two ring methylene chains.supported

Synthesis of 15 N-alkyl-arylcyclohexylamines including 3-MeO-PCE and 3-MeO-PCPr. Analytical characterizations via GC-MS, HPLC-MS, NMR, UV, IR. dta.1861