3-MeO-PCMo

Claim in safety — inconclusiveinconclusiveworking →

Claim in safety — inconclusiveinconclusiveworking →

A fatal case in the Netherlands involved a blood concentration of 152 µg/L 3-MeO-PCP in combination with amphetamine and alcohol; death was not definitively attributed to 3-MeO-PCP alone.supported

Fatal case involving 3-MeO-PCP (152 µg/L whole blood), amphetamine, and alcohol. First fatal case in Netherlands. j.jflm.2019.05.011

Delirium and agitation persisted to 24 hours post-admission.supported

Delirium/agitation at 24h. j.forsciint.2016.12.028

Additional non-fatal intoxication cases were documented by the STRIDA project in Sweden from mid-2013, and a case series with literature review was published from France involving two intoxication episodes in the same patient.partially supported

Case series from Sweden STRIDA project with clinical and bioanalytical data from analytically confirmed non-fatal intoxications with 3-MeO-PCP and 4-MeO-PCP. 15563650.2015.1079325

Additional non-fatal intoxication cases were documented by the STRIDA project in Sweden from mid-2013, and a case series with literature review was published from France involving two intoxication episodes in the same patient.supported

Reports 2 intoxication cases in the same patient and reviews manifestations of intoxication. md.0000000000018295

Urological (chronic): Ketamine-induced cystitis involves direct urothelial apoptosis through a non-NMDA receptor-mediated pathway. Whether 3-MeO-PCMo or other arylcyclohexylamines produce analogous urotoxicity with chronic use is unknown.supported

Ketamine induces urothelial apoptosis via NMDAR-independent mechanism involving purinergic P2Y receptors and mitochondrial pathway. j.ajpath.2015.12.014

Claim in safety — inconclusiveinconclusiveworking →

Acute and persistent psychosis has been documented following 3-MeO-PCP usesupported

NPS psychopathological consequences review including dissociatives. s0033291719001727

Dependence: PCP analogues demonstrate reinforcing properties in animal self-administration paradigms, driven by dopaminergic disinhibition via NMDA receptor hypofunctionsupported

Landmark review of PCP pharmacology including NMDA receptor hypofunction and dopaminergic effects. s0893-133x(98)00060-8

Claim in safety — inconclusiveinconclusiveworking →

Every documented fatality involving 3-MeO-PCP included co-ingestion of CNS depressants — alcohol in all cases, with additional substances in somesupported

Fatal case involving 3-MeO-PCP (152 µg/L whole blood), amphetamine, and alcohol. j.jflm.2019.05.011

Claim in safety — not_supportednot supportedworking →

Serotonergic agents: If 3-MeO-PCMo possesses meaningful SERT affinity — as documented for related PCP analogues — combination with MAO inhibitors, SSRIs, or other serotonergic drugs could potentiate serotonergic effectssupported

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

Psychotic disorders (personal or family history): PCP-class NMDA antagonists are established psychotomimetics. Risk of precipitating or exacerbating psychosis is high.supported

Landmark review of PCP pharmacology including NMDA receptor hypofunction and dopaminergic effects. s0893-133x(98)00060-8

Claim in safety — inconclusiveinconclusiveworking →

Hepatic impairment: Metabolism via polymorphic CYP enzymes (inferred from 3-MeO-PCP data) means impaired hepatic function could prolong drug exposure.supported

CYP enzyme involvement identified. 1570159x14666161018151716

Claim in safety — inconclusiveinconclusiveworking →

This places 3-MeO-PCMo approximately 12-fold weaker than PCP and comparable to ketamine at the NMDA receptor.supported

3-MeO-PCMo showed moderate NMDAR affinity comparable to ketamine, ~12-fold lower than PCP. dta.2213

Claim in pharmacology — inconclusiveinconclusiveworking →

Claim in pharmacology — inconclusiveinconclusiveworking →

Colestock et al. (2018) characterized 3-MeO-PCMo across 46 CNS receptor targets using (+)-[³H]-MK-801 displacement in rat forebrain membrane preparationssupported

46 CNS receptors. In vitro MK-801 binding at rat forebrain NMDAR. dta.2213

Claim in pharmacology — inconclusiveinconclusiveworking →

Roth et al. (2013) demonstrated high sigma receptor affinity for the closely related 3-MeO-PCP and 4-MeO-PCP via the NIMH Psychoactive Drug Screening Program, and methoxydine — a structurally related arylcyclohexylamine — acts as an agonist at both sigma-1 and sigma-2 receptorssupported

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

Roth et al. (2013) demonstrated high sigma receptor affinity for the closely related 3-MeO-PCP and 4-MeO-PCP via the NIMH Psychoactive Drug Screening Program, and methoxydine — a structurally related arylcyclohexylamine — acts as an agonist at both sigma-1 and sigma-2 receptorssupported

Methoxydine acts as NMDA antagonist...and agonist at sigma-1, sigma-2, and opioid receptors. j.mehy.2013.03.030

The Colestock et al. (2018) screening of 46 receptors may include sigma binding data, but these values are not reported in the published abstract.supported

Pharmacological characterization of 3-MeO-PCMo and five analogues at 46 CNS receptors. In vitro MK-801 binding at rat forebrain NMDAR. dta.2213

Serotonin transporter (SERT): Roth et al. (2013) found appreciable SERT affinities for methoxetamine and PCP analoguessupported

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

Downstream dopaminergic effects: NMDA receptor hypofunction in prefrontal cortical interneurons disinhibits mesolimbic dopaminergic signaling — a mechanism established for PCP and its classsupported

Landmark review of PCP pharmacology including NMDA receptor hypofunction and dopaminergic effects. s0893-133x(98)00060-8

Metabolic pathway data are inferred from the closely related 3-meo-pcp (same 3-methoxyphenyl-cyclohexyl scaffold, piperidine instead of morpholine), studied by Michely et al. (2017) using rat urine and human liver microsome preparations:supported

Metabolic fate of 3-MeO-PCP and 3-MeO-PCPy in rat urine and human liver microsomes. 1570159x14666161018151716

Claim in pharmacology — inconclusiveinconclusiveworking →

Claim in pharmacology — inconclusiveinconclusiveworking →

Colestock et al. (2018) screened the compound at 46 CNS receptor targets using radioligand displacement assays in rat forebrain preparationssupported

46 CNS receptors. In vitro MK-801 binding at rat forebrain NMDAR. dta.2213

The Ki value of approximately 253 nM places 3-MeO-PCMo approximately 12-fold weaker than PCP and in the same potency range as ketaminepartially supported

3-MeO-PCMo showed moderate NMDAR affinity comparable to ketamine, ~12-fold lower than PCP. dta.2213

This rank order demonstrates that meta-position substitution on the phenyl ring (positions 3-) preserves or enhances NMDA affinity relative to the unsubstituted parent, while para-substitution (position 4-) substantially diminishes it.supported

Pharmacological characterization of 3-MeO-PCMo and five analogues at 46 CNS receptors. dta.2213

3-MeO-PCP and 4-MeO-PCP: High affinity for sigma receptors demonstrated via the NIMH Psychoactive Drug Screening Program.supported

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

Methoxydine: Characterized as an agonist at both sigma-1 and sigma-2 receptors.supported

Methoxydine acts as NMDA antagonist...and agonist at sigma-1, sigma-2, and opioid receptors. j.mehy.2013.03.030

PCP class: Sigma receptor binding is a well-established secondary pharmacological activity across the arylcyclohexylamine class.supported

Review of sigma binding sites including PCP receptor and their role in arylcyclohexylamine pharmacology. pmid:2172677

The Colestock et al. (2018) 46-receptor screen may contain sigma binding data for 3-MeO-PCMo, but values beyond the NMDA receptor are not reported in the published abstract.supported

Pharmacological characterization at 46 CNS receptors. In vitro MK-801 binding at rat forebrain NMDAR. dta.2213

SERT affinity has been documented for several methoxylated PCP analogues, but whether 3-MeO-PCMo possesses meaningful serotonin transporter binding has not been determinedsupported

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

It acts as a non-competitive NMDA receptor antagonist with a Ki of approximately 253 nM at the PCP binding site — roughly 12-fold weaker than PCP and comparable to ketaminepartially supported

3-MeO-PCMo showed moderate NMDAR affinity comparable to ketamine, ~12-fold lower than PCP. dta.2213

The sole published pharmacological characterization — Colestock et al. (2018) — synthesized and screened the compound across 46 CNS receptor targets, confirming NMDA receptor antagonism as its primary mechanismsupported

Pharmacological characterization of 3-MeO-PCMo and five analogues at 46 CNS receptors. In vitro MK-801 binding at rat forebrain NMDAR. dta.2213

Sigma receptor agonism — established for the closely related 3-MeO-PCP and methoxydine but not directly confirmed for 3-MeO-PCMo — may contribute additional stimulant and mood-elevating qualitiessupported

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

Sigma receptor agonism — established for the closely related 3-MeO-PCP and methoxydine but not directly confirmed for 3-MeO-PCMo — may contribute additional stimulant and mood-elevating qualitiessupported

Methoxydine acts as NMDA antagonist...and agonist at sigma-1, sigma-2, and opioid receptors. j.mehy.2013.03.030

Claim in summary — inconclusiveinconclusiveworking →

All toxicological inference derives from 3-MeO-PCP, where fatalities have been documented — invariably involving co-ingestion of CNS depressantssupported

Seven deaths and one non-fatal intoxication involving 3-MeO-PCP in Sweden during March 2014 to June 2016. j.forsciint.2017.02.034

All toxicological inference derives from 3-MeO-PCP, where fatalities have been documented — invariably involving co-ingestion of CNS depressantssupported

Fatal case involving 3-MeO-PCP (152 µg/L whole blood), amphetamine, and alcohol. j.jflm.2019.05.011

Claim in chemistry — inconclusiveinconclusiveworking →

The PCMo (phenylcyclohexylmorpholine) series explored by Colestock et al. (2018) included six positional isomers and ring-substituted variants: PCMo (unsubstituted), 2-MeO-PCMo, 3-MeO-PCMo, 4-MeO-PCMo, 3,4-MD-PCMo (methylenedioxy), and 3-Me-PCMo (methyl).supported

3-MeO-PCMo and five analogues (2-MeO-PCMo, 4-MeO-PCMo, 3,4-MD-PCMo, 3-Me-PCMo, PCMo). dta.2213

The methoxy group at the meta position of the phenyl ring is a key pharmacophoric element — its position influences NMDA receptor binding affinity, as demonstrated by the potency rank order across the PCMo isomer series.supported

Pharmacological characterization of 3-MeO-PCMo and five analogues...at 46 CNS receptors. In vitro MK-801 binding at rat forebrain NMDAR. dta.2213

Colestock et al. (2018) synthesized and characterized it analytically (NMR, mass spectrometry) but did not report physical constants beyond spectral data.partially supported

All compounds synthesized and characterized by chromatographic, MS, and spectroscopic techniques. dta.2213

Positional isomers within the PCMo series (2-MeO, 3-MeO, 4-MeO) require careful chromatographic and spectroscopic techniques to distinguish, as they share identical molecular formulae and similar fragmentation patternssupported

All compounds synthesized and characterized by chromatographic, MS, and spectroscopic techniques. dta.2213

Confirmation requires gas chromatography–mass spectrometry (GC-MS) or liquid chromatography–high-resolution mass spectrometry (LC-HRMS)supported

Detectability in urine by GC-MS and LC-HRMS. 1570159x14666161018151716

Metabolic data are extrapolated from Michely et al. (2017), who characterized the metabolic fate of 3-MeO-PCP and 3-MeO-PCPy (rolicyclidine analogue) using rat urine and human liver microsome incubations.supported

Metabolic fate of 3-MeO-PCP and 3-MeO-PCPy in rat urine and human liver microsomes. 1570159x14666161018151716

Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →

Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →

Positional isomers within the PCMo series require careful chromatographic separation for unambiguous identification.supported

All compounds synthesized and characterized by chromatographic, MS, and spectroscopic techniques. dta.2213

Direct head-to-head pharmacological comparison data for 3-MeO-PCMo exist only within the PCMo analogue series characterized by Colestock et al. (2018)supported

Pharmacological characterization of 3-MeO-PCMo and five analogues at 46 CNS receptors. dta.2213

Claim in comparative-pharmacology — inconclusiveinconclusiveworking →

Both compounds exhibit comparable Ki values at the NMDA receptor PCP binding site (~253 nM for 3-MeO-PCMo versus ~660 nM for racemic ketamine and ~130 nM for S-ketamine)partially supported

3-MeO-PCMo showed moderate NMDAR affinity comparable to ketamine. dta.2213

The Colestock et al. (2018) study provides the only published intra-series comparison:supported

Pharmacological characterization of 3-MeO-PCMo and five analogues at 46 CNS receptors. dta.2213

The compound emerged on online research chemical markets in the mid-2010s as one of a proliferating series of arylcyclohexylamine novel psychoactive substances (NPS) derived from phencyclidine and its methoxylated analoguessupported

Pharmacological characterization of 3-MeO-PCMo and five analogues...All compounds synthesized and characterized. dta.2213

Claim in history — not_supportednot supportedworking →

Claim in history — inconclusiveinconclusiveworking →

Claim in history — inconclusiveinconclusiveworking →

The following mechanisms are inferred from the compound's confirmed NMDA receptor antagonism and from established neuroscience of PCP-site NMDA antagonists.supported

3-MeO-PCMo showed moderate NMDAR affinity comparable to ketamine, ~12-fold lower than PCP. dta.2213

PCP and ketamine produce measurable reductions in thalamocortical connectivity, dissociating sensory input processing from higher-order cortical integrationsupported

Landmark review of PCP pharmacology including NMDA receptor hypofunction and dopaminergic effects. s0893-133x(98)00060-8

Prefrontal disinhibition and dopaminergic activation: NMDA receptor hypofunction on GABAergic interneurons in the prefrontal cortex reduces inhibitory tone, leading to paradoxical cortical excitation and downstream disinhibition of mesolimbic dopamine release from the ventral tegmental area (VTA) to the nucleus accumbens (NAc)supported

Landmark review of PCP pharmacology including NMDA receptor hypofunction and dopaminergic effects. s0893-133x(98)00060-8

Claim in clinical-evidence — inconclusiveinconclusiveworking →

Its only published pharmacological characterization is a forensic and analytical study (Colestock et al. 2018) motivated by its appearance on research chemical markets, not by therapeutic intent.supported

Syntheses, analytical and pharmacological characterizations of the 'legal high' 4-[1-(3-methoxyphenyl)cyclohexyl]morpholine (3-MeO-PCMo). dta.2213