Methoxetamine

2-(ethylamino)-2-(3-methoxyphenyl)cyclohexan-1-one

Overview

Methoxetamine belongs to Dissociatives / Arylcyclohexylamines.

Key safety note: Methoxetamine is considerably more potent and much longer-acting than ketamine, and it was aggressively, and falsely, marketed as a 'bladder-safe' ketamine substitute.[3][4]
Effects
Subjective effects vary. What a substance feels like depends on dose, individual physiology, mindset, and setting. The points below describe commonly reported effects, not guaranteed, uniform, or desirable outcomes.
  • Dissociation with depersonalisation and derealisation, dreamlike and anaesthetic states, and a euphoria and mental space often described as clearer or more stimulating than ketamine's.
  • Sensory and motor changes: numbness, visual and tactile disconnection, and at higher doses the immersive 'hole'. Ataxia, slurred speech and nystagmus.
  • Sympathetic stimulation (raised heart rate and blood pressure). After-effects can include lingering confusion, dissociation and low mood, and, after a cerebellar reaction, days of unsteadiness.
Dosing & duration
Harm-reduction note: These are commonly cited reference ranges, not a recommendation or a “safe” dose. Potency, purity, body chemistry, tolerance, and drug combinations vary widely. Start low, go slow, wait for full effects before redosing, and never assume an unknown product matches these figures. Missing data is not evidence of safety.

Insufflated, oral, sublingual or rectal. Values below are approximate ORAL figures. MXE is potent and much longer-acting than ketamine.. MXE is potent and long-acting (4–6 h oral) with a slow onset, and its steep dose–response makes overshooting easy: start very low, use an accurate milligram scale, and wait well beyond the expected onset before considering a redose (delayed onset is a common cause of overdose). Insufflated doses are a little lower and faster. Avoid combining with other depressants or stimulants, and never dose in an unsafe setting: heavy dissociation removes coordination and awareness.

Dose ranges

Threshold

5 mg

Light

10–25 mg

Common

25–45 mg

Strong

45–70 mg

Heavy

70 mg +

Duration

onset

15–30 min (oral), 5–20 min insufflated

total

4–6 h (oral)

after effects

6–48 h

Chemical & Physical Properties
FormulaC15H21NO2
Molar mass247.33 g/mol
StateSolid (usually the hydrochloride salt, crystalline)
Melting pointNot reported
Boiling pointNot reported
DensityNot reported
Vapor pressureNot reported
pKaNot reported
LogP2.3 (predicted, XLogP3)
SolubilityNot reported
Refractive indexNot reported
Identifiers & Synonyms
CASNot reported
CAS (enantiomer)
PubChem CID52911279
InChIKeyLPKTWLVEGBNOOX-UHFFFAOYSA-N
InChIInChI=1S/C15H21NO2/c1-3-16-15(10-5-4-9-14(15)17)12-7-6-8-13(11-12)18-2/h6-8,11,16H,3-5,9-10H2,1-2H3
SMILESCCNC1(CCCCC1=O)C2=CC(=CC=C2)OC

Synonyms

  • MXE
  • Mexxy
  • 3-MeO-2-Oxo-PCE
Pharmacodynamics & Biochemistry

Methoxetamine (MXE, 'Mexxy') is a dissociative anaesthetic of the arylcyclohexylamine class: a designer analogue of ketamine carrying an N-ethyl group (instead of N-methyl), a 3-methoxy ring substituent and a cyclohexanone core. Like ketamine and PCP it is a non-competitive NMDA-receptor antagonist, binding the PCP/MK-801 channel site to block glutamatergic transmission. Roth et al. (2013) measured a Ki of 337 ± 76 nM at the NMDA PCP site, comparable to ketamine. This blockade produces the characteristic dose-dependent dissociation, analgesia, anaesthesia and, at high doses, the immersive 'hole' state. Unlike ketamine, MXE was designed to add serotonergic activity: in the same study it showed submicromolar affinity for the serotonin transporter (SERT) while being essentially inactive at the dopamine and noradrenaline transporters (Ki > 10 µM). That serotonergic component, together with a longer duration and greater potency than ketamine, gives MXE a somewhat different, often more stimulating and euphoric character. It is used as the racemate.

Biological targets

  • NMDA
  • SERT

Binding & functional measurements

TargetMeasurementSpecies
NMDA receptorKi 259 nMRat
Serotonin transporterKi 481 nMHuman
Pharmacokinetics
BioavailabilityNot reported
TmaxNot reported
Half-life≈3–6 h (long relative to ketamine)
VdNot reported
Protein bindingNot reported
MetabolismHepatic: O-demethylation (to O-desmethyl-methoxetamine/normethoxetamine) and N-deethylation, plus hydroxylation (CYP-mediated)
ExcretionRenal
Toxicology & Safety
Harm-reduction note: Toxicity and risk depend on dose, route, purity, combinations, setting, and individual health factors. Missing harms should never be interpreted as evidence of safety.

Not reported

Methoxetamine is considerably more potent and much longer-acting than ketamine, and it was aggressively, and falsely, marketed as a 'bladder-safe' ketamine substitute. Its long duration and steep dose–response make overshooting easy: a few extra milligrams can push a user into heavy dissociation, the immersive 'M-hole', catatonia, vomiting with aspiration risk, and dangerous loss of coordination and awareness. MXE causes more cardiovascular stimulation than ketamine (tachycardia and hypertension are common) and has produced a distinctive acute cerebellar toxicity, ataxia, slurred speech, nystagmus and unsteady gait, that can last for days. The 'bladder-sparing' claim was not borne out: animal studies show ketamine-like bladder inflammation and fibrosis, so urinary-tract damage from regular use should be expected. It is strongly dissociative and disinhibiting, so injuries and dangerous behaviour occur. The delayed onset tempts compulsive redosing, a common cause of accidental overdose, and combining it with other depressants (alcohol, benzodiazepines, opioids, GHB) or stimulants sharply raises the risk. Deaths and hospitalisations have occurred, usually with high doses or drug combinations.[3][4]

Legal Status
Legal note: Legal status can change over time and may vary by country, region, formulation, analogue status, prescription context, and enforcement practice. Always confirm with current official sources before relying on this section.
Interactions & Contraindications

Drug interactions

Alcohol, Benzodiazepines, Opioids, GHB / GBL Additive sedation and airway or respiratory risk, worsened by vomiting.[3][4]
Stimulants (amphetamines, cocaine) Mask the dissociation and add cardiovascular strain.[4]
MAOIs, SSRIs A theoretical serotonin-toxicity risk given MXE's serotonin-transporter activity.[2][3]

Contraindications

Cardiovascular disease, hypertension or arrhythmia[3]
Personal or family history of psychosis, schizophrenia or bipolar disorder[3]
Pre-existing bladder or urinary-tract disease, or drug-induced cystitis[3]
Combining with alcohol or other CNS depressants concurrent depressants or serotonergic medication.[3]
Settings where impairment or dissociation risks injury (driving, water, heights) anything needing coordination or alertness, e.g. driving.[4]
Usage & Context
  • A recreational dissociative and one of the first 'research chemical' ketamine substitutes to be widely sold online (around 2010–2012), taken for dissociation, euphoria, anaesthesia and out-of-body / 'hole' experiences: insufflated, swallowed, or used sublingually or rectally.
  • Marketed as a legal, supposedly 'bladder-safe' alternative to ketamine. Its rapid spread and associated harms made it an early test case for emergency drug legislation: the first substance placed under a UK Temporary Class Drug Order (2012).
  • No accepted medical use. Now controlled in most jurisdictions.
Sources & Evidence

Further Information