Methoxphenidine
1-[1-(2-methoxyphenyl)-2-phenylethyl]piperidine
Overview
Methoxphenidine belongs to Dissociatives.
Effects
- Dissociation with depersonalisation and derealisation, detachment from the body, euphoria, conceptual/'philosophical' thinking and increased music appreciation: often described as clearer-headed than other dissociatives.
- Tactile and motor disconnection, numbness, ataxia and loss of coordination. At higher doses visual distortions, hallucinations and an anaesthetic 'hole'.
- Sympathetic stimulation (raised heart rate and blood pressure). The comedown and after-effects can include confusion, lingering dissociation and low mood.
Dosing & duration
Oral or insufflated. Values below are approximate ORAL figures. MXP is long-acting with a slow onset.. MXP has a slow onset (30–60 min) and a long duration (6–8 h), so redosing before the first dose is felt is a common cause of overdose: wait well beyond the expected onset. It is sold as a research chemical of uncertain purity, so start low with an accurate milligram scale, and avoid combining with other depressants or stimulants.
Dose ranges
30 mg
50–75 mg
75–120 mg
120–150 mg
150 mg +
Duration
30–60 min
6–8 h
1–3 h
Chemical & Physical Properties
| Formula | C20H25NO |
| Molar mass | 295.4 g/mol |
| State | Solid (usually the hydrochloride salt, crystalline) |
| Melting point | Not reported |
| Boiling point | Not reported |
| Density | Not reported |
| Vapor pressure | Not reported |
| pKa | Not reported |
| LogP | 4.6 (predicted, XLogP3) |
| Solubility | Not reported |
| Refractive index | Not reported |
Identifiers & Synonyms
| CAS | Not reported |
| CAS (enantiomer) | |
| PubChem CID | 67833251 |
| InChIKey | QXXCUXIRBHSITD-UHFFFAOYSA-N |
| InChI | InChI=1S/C20H25NO/c1-22-20-13-7-6-12-18(20)19(21-14-8-3-9-15-21)16-17-10-4-2-5-11-17/h2,4-7,10-13,19H,3,8-9,14-16H2,1H3 |
| SMILES | COC1=CC=CC=C1C(CC2=CC=CC=C2)N3CCCCC3 |
Synonyms
- MXP
- 2-MeO-Diphenidine
- 2-MeO-DPH
- Methoxydiphenidine
Pharmacodynamics & Biochemistry
Methoxphenidine (MXP, 2-MeO-diphenidine) is a dissociative of the diarylethylamine class, the 2-methoxy analogue of diphenidine, and, like ketamine and PCP, an antagonist of the NMDA glutamate receptor. It is an open-channel blocker: once glutamate opens the receptor, MXP binds within the pore at the PCP/dizocilpine (MK-801) site and blocks cation flux in a use- and voltage-dependent way. Wallach et al. (2016) measured an NMDA affinity of Ki ≈ 36 nM ([3H]MK-801, rat forebrain): high, though somewhat weaker than diphenidine (~18 nM). Anecdotally MXP is nonetheless the more orally potent of the two, probably reflecting better oral bioavailability. Beyond the NMDA channel it is fairly selective: it binds the dopamine transporter only weakly (Ki ≈ 2.9 µM), shows moderate affinity at the σ1/σ2 receptors, and has no meaningful serotonin-transporter activity. This NMDA-dominant profile produces the dissociative state: detachment from body and surroundings, analgesia, disordered sensory integration and, at high doses, anaesthesia, and MXP is noted for an unusually long duration and a comparatively 'clear-headed' character. It is used as the racemate.
Biological targets
- NMDA
Binding & functional measurements
| Target | Measurement | Species |
|---|---|---|
| NMDA receptor | Ki 36 ± 3.7 nM | Rat |
| Dopamine transporter | Ki 2,915 nM | Human |
Pharmacokinetics
| Bioavailability | Not reported |
| Tmax | Not reported |
| Half-life | Not established in humans. Reported subjective effects of 6–8 h are not an elimination half-life. |
| Vd | Not reported |
| Protein binding | Not reported |
| Metabolism | Hepatic: O-demethylation, aromatic/aliphatic hydroxylation and N-dealkylation, then conjugation |
| Excretion | Renal |
Toxicology & Safety
Not reported
Methoxphenidine is a potent, long-acting dissociative sold only as an unregulated research chemical, so purity and dose are uncertain and overshooting is easy: especially given its slow onset (30–60 min), which tempts dangerous redosing before the first dose is felt. Effects include heavy dissociation, ataxia and loss of coordination, confusion, nausea, and, via its sympathomimetic action, raised heart rate and blood pressure (hypertension and tachycardia are typical features of MXP intoxication). High doses can produce an anaesthetic 'hole' with immobility and vomiting (aspiration risk), agitation and acute psychosis. A number of psychotic episodes and at least three fatalities have been reported, and MXP was implicated in a widely reported homicide. Its long duration and delayed onset strongly encourage compulsive redosing, and combining it with other depressants (alcohol, benzodiazepines, opioids) or stimulants sharply raises the danger.[4][3]
Legal Status
US: Not federally scheduled. UK: Class B / Schedule 1. DE: NpSG structural assessment required
Interactions & Contraindications
Drug interactions
Contraindications
No interactions or contraindications listed.
Usage & Context
- A recreational dissociative sold from around 2013 as an unregulated 'research chemical' and ketamine/diphenidine substitute, usually swallowed or insufflated, valued for a long, comparatively clear-headed dissociative state.
- It emerged as one of the diarylethylamine dissociatives that filled the gap left when arylcyclohexylamine (ketamine-type) dissociatives were banned. It has no medical use.
- It has been linked to hospital presentations, impaired driving and fatalities, and is now restricted in many countries.
Sources & Evidence
- PubChem: Methoxphenidine (CID 67833251) — identifiers & computed properties
- Wallach J, Kang H, Colestock T, et al. (2016). Pharmacological Investigations of the Dissociative 'Legal Highs' Diphenidine, Methoxphenidine and Analogues. PLoS One 11:e0157021.
PMID 27314670 · doi:10.1371/journal.pone.0157021
- Helander A, Beck O, Bäckberg M (2015). Intoxications by the dissociative new psychoactive substances diphenidine and methoxphenidine. Clin Toxicol (Phila) 53:446-53.
PMID 25881797 · doi:10.3109/15563650.2015.1033630
- Wikipedia: Methoxphenidine — pharmacology (diarylethylamine NMDA antagonist), harms & legal status CC BY-SA 4.0
- PsychonautWiki: Methoxphenidine — dosage, duration & subjective effects CC BY-SA 4.0
- DEA Diversion Control Division: Controlled Substance Schedules (methoxphenidine is not federally scheduled)
- UK Psychoactive Substances Act 2016 — blanket ban on psychoactive substances (legislation.gov.uk) OGL v3.0
- Anlage II BtMG: individual substance listings do not determine NpSG structural coverage
- Home Office: Class B and Schedule 1 control of diarylethylamine dissociatives (2024) OGL v3.0
- NpSG: current structural definitions and Anlage 2 (checked 18 September 2026)