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