DMXE

Seizures: Documented in acute MXE intoxication (inhalation route), presenting alongside sinus bradycardia (48 bpm), ST-segment elevation, and hyponatremia (127 mmol/L; MXE serum concentration 30 μg/L, urine 408 μg/L)partially supported

Single MXE inhalation case: 21-year-old man found collapsed after suspected seizure. Sinus bradycardia, ST-segment elevation, hyponatremia. Serum 30 µg/L, urine 408 µg/L. bku052

Claim in safety — not_supportednot supportedworking →

Rhabdomyolysis: The first laboratory-confirmed case of 3-methyl-PCP use (a compound sharing DMXE's 3-methylphenyl ring substitution, differing in the nitrogen ring system and ketone) produced rhabdomyolysis and acute kidney injury. This structural parallel warrants caution but does not constitute direct evidence of rhabdomyolysis risk for DMXE.supported

First laboratory-confirmed use of 3-methyl-PCP (a novel arylcyclohexylamine) causing rhabdomyolysis and acute kidney injury. s13181-026-01122-y

Fatal outcome: A fatal case involving O-PCE (N-ethyldeschloroketamine) — a compound sharing DMXE's ethylamino group and cyclohexanone core — occurred in combination with venlafaxine (femoral blood concentration 375 μg/L). No fatalities attributed to DMXE alone or in combination have been reported.partially supported

Fatal case of 52-year-old man who abused N-ethyldeschloroketamine (2-Oxo-PCE/O-PCE) and venlafaxine. Tissue concentration data provided across multiple specimens. bky063

Urological damage: Chronic heavy ketamine use causes ketamine-induced uropathy (KIU), a progressive lower urinary tract syndrome characterized by inflammation, fibrosis, reduced bladder capacity, and in severe cases ureteral stenosis and renal failuresupported

Systematic review of ketamine-induced uropathy (KIU): clinical presentation, pathophysiology, and treatments. Ketamine is a dissociative anesthetic; recreational abuse leads to urinary tract complications. nau.24341

Claim in safety — inconclusiveinconclusiveworking →

Neurological damage: Acute MXE intoxication (single intravenous dose) produced a substance-induced psychotic disorder with bilateral dorsolateral prefrontal cortex (DLPFC) metabolic deficit on ¹⁸F-FDG PET/CT, accompanied by severe dissociative symptoms, reduced motivation, and impaired verbal fluency and working memorysupported

Case of 23-year-old man who developed substance-induced psychotic disorder after IV MXE injection. 18F-FDG PET/CT showed bilateral DLPFC metabolic deficit. Severe dissociative symptoms, reduced motivation, impaired verbal fluency and working memory. 02791072.2019.1578444

Persistent psychosis and cognitive impairment have also been documented following 3-MeO-PCP use, with PET/CT evidence of cerebral metabolic changessupported

3-MeO-PCP-induced psychotic disorder in 29-year-old man. PET/CT case. Persistent psychotic symptoms and cognitive impairment documented. ph17040452

Claim in safety — inconclusiveinconclusiveworking →

Substance-induced psychotic disorder has been documented for both MXE and 3-MeO-PCP within the arylcyclohexylamine class, with cases persisting beyond the acute intoxication periodsupported

Case of 23-year-old man who developed substance-induced psychotic disorder after IV MXE injection. 18F-FDG PET/CT showed bilateral DLPFC metabolic deficit. 02791072.2019.1578444

Substance-induced psychotic disorder has been documented for both MXE and 3-MeO-PCP within the arylcyclohexylamine class, with cases persisting beyond the acute intoxication periodsupported

3-MeO-PCP-induced psychotic disorder in 29-year-old man. Persistent psychotic symptoms and cognitive impairment documented. ph17040452

Serotonergic agents (SSRIs, SNRIs, tramadol, MAO inhibitors): If DMXE retains SERT affinity analogous to MXE, co-administration with serotonergic drugs carries risk of serotonin syndromesupported

Additional affinities for serotonin transporter and sigma receptors noted. journal.pone.0059334

The fatal case involving O-PCE (structurally related to DMXE) combined with the SNRI venlafaxine underscores this concernsupported

Fatal case of 52-year-old man who abused N-ethyldeschloroketamine (2-Oxo-PCE/O-PCE) and venlafaxine. bky063

Psychotic disorders (personal or family history): NMDA antagonists are psychotomimetic agents; arylcyclohexylamine use has produced persistent psychosis in documented casessupported

Case of 23-year-old man who developed substance-induced psychotic disorder after IV MXE injection. 02791072.2019.1578444

Psychotic disorders (personal or family history): NMDA antagonists are psychotomimetic agents; arylcyclohexylamine use has produced persistent psychosis in documented casessupported

Persistent psychotic symptoms and cognitive impairment documented. ph17040452

Concurrent SNRI/SSRI use at high doses: Serotonin syndrome risk if DMXE possesses SERT activity; O-PCE + venlafaxine fatality is the most relevant casesupported

Fatal case of 52-year-old man who abused N-ethyldeschloroketamine (2-Oxo-PCE/O-PCE) and venlafaxine. bky063

Claim in safety — not_supportednot supportedworking →

Renal impairment: Reduced clearance of compound and metabolites; rhabdomyolysis risk by structural parallel with 3-methyl-PCPsupported

First laboratory-confirmed use of 3-methyl-PCP (a novel arylcyclohexylamine) causing rhabdomyolysis and acute kidney injury. s13181-026-01122-y

Hepatic impairment: Predicted CYP2B6/CYP3A4 metabolism; impaired hepatic function may alter drug levels unpredictablysupported

Initial N-deethylation catalyzed by CYP2B6 and CYP3A4 in humans. s00216-013-7051-6

History of seizure disorder: Seizures documented in MXE intoxicationsupported

21-year-old man found collapsed after suspected seizure. Seizure recurred during hospitalization. bku052

Lower urinary tract disease: Class-level risk of arylcyclohexylamine uropathy with repeated exposuresupported

Systematic review of ketamine-induced uropathy (KIU): clinical presentation, pathophysiology, and treatments. Recreational abuse leads to urinary tract complications. nau.24341

Claim in summary — inconclusiveinconclusiveworking →

The compound inhibits NMDA-mediated glutamatergic transmission with an IC₅₀ of 0.679 μM in mouse neuronal preparations, potency comparable to its parent compound methoxetamine (MXE; IC₅₀ = 0.524 μM)supported

NMDA receptor IC50 values measured for methoxetamine derivatives including DMXE (IC50 0.679 µM), MXE (0.524 µM)... Patch-clamp recordings in NMDAR-expressing cartwheel interneurons of mice. j.jphs.2022.09.005

Claim in summary — inconclusiveinconclusiveworking →

Claim in summary — inconclusiveinconclusiveworking →

Claim in summary — inconclusiveinconclusiveworking →

Claim in summary — inconclusiveinconclusiveworking →

Class-level risks include seizures, cardiovascular disturbance (documented for MXE), substance-induced psychosis, and progressive lower urinary tract damage with chronic heavy use (established for ketamine)supported

21-year-old man found collapsed after suspected seizure. Sinus bradycardia, ST-segment elevation, hyponatremia. Seizure recurred during hospitalization. bku052

Class-level risks include seizures, cardiovascular disturbance (documented for MXE), substance-induced psychosis, and progressive lower urinary tract damage with chronic heavy use (established for ketamine)supported

Case of 23-year-old man who developed substance-induced psychotic disorder after IV MXE injection. 02791072.2019.1578444

Class-level risks include seizures, cardiovascular disturbance (documented for MXE), substance-induced psychosis, and progressive lower urinary tract damage with chronic heavy use (established for ketamine)supported

Systematic review of ketamine-induced uropathy (KIU): clinical presentation, pathophysiology, and treatments. Ketamine is a dissociative anesthetic; recreational abuse leads to urinary tract complications. nau.24341

Claim in neuroscience — inconclusiveinconclusiveworking →

This AMPA receptor potentiation drives rapid synaptogenesis via downstream BDNF release and mTOR pathway activation — the mechanism underlying ketamine's rapid antidepressant effectssupported

AMPAR activation and BDNF increases as downstream mechanisms. 7854_2022_313

MXE analogs have also demonstrated antidepressant-like behavioral effects via AMPA and 5-HT₂ receptor activation in animal modelssupported

Three novel MXE analogs produce rapid antidepressant effects via AMPA and 5-HT2 receptor activation. s00213-019-05219-x

Claim in neuroscience — inconclusiveinconclusiveworking →

Claim in neuroscience — inconclusiveinconclusiveworking →

Does DMXE inhibit the serotonin transporter (SERT)? If so, this would place DMXE closer to MXE (which possesses SERT affinity) than to ketamine in its pharmacological profile and would have significant implications for interaction risk with serotonergic drugs.supported

Additional affinities for serotonin transporter and sigma receptors noted. journal.pone.0059334

What brain regions show altered metabolic activity during acute DMXE intoxication? MXE has been associated with bilateral dorsolateral prefrontal cortex metabolic deficit on PET/CT.supported

18F-FDG PET/CT showed bilateral DLPFC metabolic deficit. 02791072.2019.1578444

Metabolic pathway predictions are derived from MXE metabolism data, which identified CYP2B6 and CYP3A4 as the primary enzymes catalyzing N-deethylation of MXE's ethylamino groupsupported

Initial N-deethylation catalyzed by CYP2B6 and CYP3A4 in humans. s00216-013-7051-6

Irie et al. (2022) provided the only published direct measurement of DMXE activity at NMDA receptors, reporting an IC₅₀ of 0.679 μM via whole-cell patch-clamp recordings in NMDAR-expressing cartwheel interneurons of the mouse dorsal cochlear nucleus. In silico molecular docking confirmed that DMXE binds at the PCP site within the NMDA channelsupported

NMDA receptor IC50 values measured for methoxetamine derivatives including DMXE (IC50 0.679 µM)... Patch-clamp recordings in NMDAR-expressing cartwheel interneurons of mice. In silico docking studies confirm binding interactions. j.jphs.2022.09.005

Irie et al. (2022) provided the only published direct measurement of DMXE activity at NMDA receptors, reporting an IC₅₀ of 0.679 μM via whole-cell patch-clamp recordings in NMDAR-expressing cartwheel interneurons of the mouse dorsal cochlear nucleus. In silico molecular docking confirmed that DMXE binds at the PCP site within the NMDA channelsupported

NMDA receptor IC50 values measured for methoxetamine derivatives including DMXE (IC50 0.679 µM)... In silico docking studies confirm binding interactions. j.jphs.2022.09.005

This potency is comparable to MXE (IC₅₀ = 0.524 μM) and methoxisopropamine (IC₅₀ = 0.661 μM), and substantially greater than the MXE metabolite N-desethyl MXE (IC₅₀ = 1.649 μM), as measured in the same assay system.supported

NMDA receptor IC50 values measured for methoxetamine derivatives including DMXE (IC50 0.679 µM), MXE (0.524 µM), methoxisopropamine (0.661 µM), N-desethyl MXE (1.649 µM)... j.jphs.2022.09.005

By structural analogy with MXE, which was profiled across 46 CNS receptor targets, DMXE may possess affinity for the serotonin transporter (SERT) — a property that contributes to MXE's reported empathogenic qualitypartially supported

MXE and 3-MeO-PCE confirmed as high affinity NMDA receptor (PCP-site) ligands. Additional affinities for serotonin transporter and sigma receptors noted. journal.pone.0059334

Claim in pharmacology — inconclusiveinconclusiveworking →

Secondary pathways likely include cyclohexyl and aryl ring hydroxylation, with Phase II conjugation (glucuronidation, sulfation) of hydroxylated metabolitessupported

MXE metabolism characterized: N-deethylation, O-demethylation, hydroxylation, glucuronidation/sulfation. s00216-013-7051-6

Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →

MXE metabolism proceeds primarily via N-deethylation (CYP2B6, CYP3A4), O-demethylation (CYP2B6, CYP2C19), and ring hydroxylation, with subsequent Phase II glucuronidation and sulfationsupported

MXE metabolism characterized: N-deethylation, O-demethylation, hydroxylation, glucuronidation/sulfation. Initial N-deethylation catalyzed by CYP2B6 and CYP3A4 in humans. s00216-013-7051-6

The predicted primary metabolic route is therefore N-deethylation to nor-DMXE (N-desethyl-DMXE), catalyzed by CYP2B6 and CYP3A4supported

Initial N-deethylation catalyzed by CYP2B6 and CYP3A4 in humans. s00216-013-7051-6

For MXE, the analogous metabolite N-desethyl MXE showed reduced NMDA antagonist potency (IC₅₀ = 1.649 μM vs. 0.524 μM for MXE), suggesting that N-deethylation may represent a deactivation pathway — but direct measurement for DMXE metabolites is lacking.supported

MXE (0.524 µM)... N-desethyl MXE (1.649 µM). j.jphs.2022.09.005

Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →

DMXE is not detected by standard immunoassay drug screening panels; definitive identification requires liquid chromatography–tandem mass spectrometry (LC-MS/MS) or gas chromatography–mass spectrometry (GC-MS).supported

Notes novel designer drugs may remain undetected by routine screening. s00204-020-02693-7

Claim in history — inconclusiveinconclusiveworking →

This pattern — novel arylcyclohexylamine analogs appearing in response to the scheduling of predecessors — is well-established within the classsupported

Historical context of PCP analogs on illicit markets since 1960s. Covers methoxetamine, deschloroketamine, and 2-fluoro-2-deschloroketamine. 164_2018_148

Tanaka et al. (2022) published the first peer-reviewed forensic characterization, identifying DMXE alongside MXPr and MXiPr in seized products in Japan using NMR spectroscopy and mass spectrometrysupported

DMXE, MXPr, and MXiPr identified in illegal products seized in Japan. Analytical data including NMR and mass spectrometry provided for forensic identification. yakushi.21-00235

The first primary pharmacological data on DMXE appeared in Irie et al. (2022), published in the Journal of Pharmacological Sciences, which measured NMDA receptor IC₅₀ values for DMXE and several MXE metabolites in mouse neuronal preparationssupported

NMDA receptor IC50 values measured for methoxetamine derivatives including DMXE (IC50 0.679 µM), MXE (0.524 µM)... Patch-clamp recordings in NMDAR-expressing cartwheel interneurons of mice. j.jphs.2022.09.005

Seibert et al. (2025) subsequently conducted the first enantioseparation of DMXE among 11 novel ketamine derivatives, using capillary electrophoresis and HPLC with chiral stationary phasessupported

Chiral separation methods developed for 11 novel ketamine derivatives including DMXE. CE and HPLC methods tested. Some compounds enantioseparated for first time due to novelty. separations12020044

Claim in comparative-pharmacology — inconclusiveinconclusiveworking →

DMXE and MXE are approximately equipotent at the NMDA receptor (IC₅₀ ratio ≈ 1.3:1), indicating that the 3-methoxy to 3-methyl substitution has minimal impact on primary target affinitysupported

DMXE (IC50 0.679 µM), MXE (0.524 µM). j.jphs.2022.09.005

N-deethylation substantially reduces potency (approximately 3-fold for MXE → N-desethyl MXE), while the O-desmethyl metabolite of MXE is the most potent compound in the series.supported

MXE (0.524 µM)... N-desethyl MXE (1.649 µM), O-desmethyl MXE (0.227 µM). j.jphs.2022.09.005

MXE has been profiled across 46 CNS receptors, revealing appreciable SERT affinity alongside NMDA antagonismpartially supported

Pharmacological profiles of novel ketamine and PCP analogues via NIMH PDSP. MXE and 3-MeO-PCE confirmed as high affinity NMDA receptor (PCP-site) ligands. Additional affinities for serotonin transporter and sigma receptors noted. journal.pone.0059334

The only published receptor-level data for DMXE derives from Irie et al. (2022), who measured functional NMDA receptor inhibition using whole-cell patch-clamp electrophysiology in mouse dorsal cochlear nucleus cartwheel interneurons.supported

Patch-clamp recordings in NMDAR-expressing cartwheel interneurons of mice. j.jphs.2022.09.005

DMXE's IC₅₀ of 0.679 μM places it within the same potency range as its parent compound MXE (IC₅₀ = 0.524 μM), indicating that replacement of the 3-methoxy group with a methyl group does not substantially diminish NMDA antagonist potencysupported

NMDA receptor IC50 values measured for methoxetamine derivatives including DMXE (IC50 0.679 µM), MXE (0.524 µM). j.jphs.2022.09.005

By structural analogy with MXE, which demonstrated appreciable SERT affinity alongside NMDA antagonism, DMXE may possess secondary serotonergic activitysupported

MXE and 3-MeO-PCE confirmed as high affinity NMDA receptor (PCP-site) ligands. Additional affinities for serotonin transporter and sigma receptors noted. journal.pone.0059334

Claim in chemistry — inconclusiveinconclusiveworking →

Seibert et al. (2025) achieved the first enantioseparation of DMXE using capillary electrophoresis (CE-UV) and HPLC with chiral stationary phases (HPLC-UV-ORD), establishing elution order and providing methods for forensic differentiation of enantiomerssupported

CE and HPLC methods tested. Enantiomer elution order determined using optical rotation detector. Some compounds enantioseparated for first time due to novelty. separations12020044

By analogy with ketamine, NMDA receptor antagonism has been associated with rapid-onset antidepressant effects, mediated through downstream AMPA receptor potentiation and BDNF-dependent synaptogenesissupported

Historical and mechanistic review of ketamine as antidepressant. AMPAR activation and BDNF increases as downstream mechanisms. 7854_2022_313

Structurally related MXE analogs (N-ethylnorketamine, 2-MeO-NEK, 4-MeO-NEK) have demonstrated antidepressant-like activity in rodent models via AMPA and 5-HT₂ receptor activationsupported

Three novel MXE analogs produce rapid antidepressant effects via AMPA and 5-HT2 receptor activation. NMDA receptor antagonism as initial mechanism. s00213-019-05219-x

DMXE satisfies both structural similarity (differs from Schedule I MXE by a single functional group substitution) and pharmacological similarity (comparable NMDA antagonist potency, IC₅₀ ratio ≈ 1.3:1)supported

NMDA receptor IC50 values measured for methoxetamine derivatives including DMXE (IC50 0.679 µM), MXE (0.524 µM). j.jphs.2022.09.005