Memantine
3,5-dimethyladamantan-1-amine
Overview
Memantine belongs to Dissociatives.
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.
- At therapeutic doses: usually little noticeable subjective effect. Some people feel mild dizziness, headache, drowsiness or a faint 'dissociative' sensation, especially during dose titration.
- Common side effects: dizziness, headache, confusion, constipation and sleepiness. Less commonly agitation, anxiety or hallucinations.
- At high, non-medical doses: PCP/ketamine-like dissociation, disorientation, hallucinations and psychosis, with a long, drawn-out and often dysphoric course.
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.
Oral (immediate-release tablets/solution and extended-release capsules). Medical use is oral only. These are therapeutic figures from the prescribing information, not recreational guidance: memantine is a prescription medicine, titrated up slowly by a clinician to limit side effects. It is cleared by the kidneys, so the dose is reduced in significant renal impairment. Its very long half-life (~60–80 h) means levels and any toxicity accumulate over days. Supratherapeutic dosing for dissociative effects is unpredictable, long-lasting and discouraged.
Dose ranges
Immediate-release start
5 mg once daily
IR titration
increase by 5 mg at weekly intervals
IR target
20 mg/day (10 mg twice daily), 14 mg/day in severe renal impairment
Extended-release (Namenda XR)
start 7 mg once daily, titrate by 7 mg/week to 28 mg once daily
Duration
onset
Tmax ~3–7 h (clinical benefit develops over weeks)
total
Dosed once or twice daily, elimination half-life ~60–80 h
after effects
Long half-life means the drug persists for days after stopping
Chemical & Physical Properties
| Formula | C12H21N |
| Molar mass | 179.3 g/mol |
| State | Solid (usually the hydrochloride salt, white crystalline) |
| Melting point | 290–295 °C (hydrochloride salt) |
| Boiling point | unavailable: true. reason: the only figure available is a software prediction (~240 °C at 1 atm) for the free base. It is not a meaningful property of the medicine (the crystalline hydrochloride salt), which decomposes/sublimes rather than boiling: no reliable experimental boiling point exists |
| Density | Not reported |
| Vapor pressure | Not reported |
| pKa | 10.27 (basic amine) |
| LogP | 3.28 |
| Solubility | Hydrochloride salt: soluble in water (the medicine is formulated as the salt) |
| Refractive index | Not reported |
Identifiers & Synonyms
| CAS | Not reported |
| CAS (enantiomer) | |
| PubChem CID | 4054 |
| InChIKey | BUGYDGFZZOZRHP-UHFFFAOYSA-N |
| InChI | InChI=1S/C12H21N/c1-10-3-9-4-11(2,6-10)8-12(13,5-9)7-10/h9H,3-8,13H2,1-2H3 |
| SMILES | CC12CC3CC(C1)(CC(C3)(C2)N)C |
Synonyms
- Namenda
- Axura
- Ebixa
Pharmacodynamics & Biochemistry
Memantine is a low-to-moderate-affinity, uncompetitive ('open-channel') NMDA-receptor antagonist. Like ketamine it enters and blocks the open NMDA-receptor channel, but it does so with fast on/off kinetics and strong voltage-dependency: it leaves the channel quickly and is expelled when the neuron depolarises normally. This lets it damp down the excessive, tonic NMDA activation thought to drive excitotoxic neuronal damage in Alzheimer's disease while largely sparing the brief, high-intensity NMDA signals that carry normal synaptic transmission and learning, which is why, unlike high-affinity blockers such as ketamine or MK-801, it is well tolerated and not strongly psychotomimetic at therapeutic doses. Its NMDA affinity is in the sub-micromolar-to-micromolar range (roughly 0.5–1 µM IC50 at synaptic receptors, and more potent, around 20 nM, at extrasynaptic receptors), far weaker than ketamine. At higher, supratherapeutic doses the channel block becomes strong enough to produce ketamine/PCP-like dissociative effects. Beyond NMDA, memantine is an antagonist at 5-HT3 (IC50 ~1 µM) and α7 nicotinic acetylcholine receptors, with weaker dopamine-D2 and sigma-1 activity. The clinical relevance of these secondary actions is uncertain.
Biological targets
- NMDA
Binding & functional measurements
| Target | Measurement | Species |
|---|---|---|
| NMDA receptor | Ki 378 ± 26 nM | Rat |
| NMDA receptor | Ki 740 ± 74 nM | Pig |
Pharmacokinetics
| Bioavailability | Not reported |
| Tmax | Not reported |
| Half-life | ≈60–80 hours |
| Vd | Not reported |
| Protein binding | Not reported |
| Metabolism | Minimal hepatic metabolism. Mostly excreted unchanged renally |
| Excretion | Not reported |
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
At the doses used for Alzheimer's disease memantine is generally well tolerated. The most common side effects are dizziness, headache, confusion and drowsiness and, less often, agitation or hallucinations, so it is titrated up slowly. Because it is cleared largely unchanged by the kidneys, the dose must be reduced in significant renal impairment, and alkaline urine (from diet or drugs) can raise its levels by slowing excretion. At supratherapeutic doses it behaves as a dissociative anaesthetic and can cause confusion, dissociation, hallucinations and psychosis. Its very long half-life (about 60–80 hours) means effects and any toxicity build up and persist for days, making it a poor and risky recreational drug. It should be combined only cautiously with other NMDA antagonists (ketamine, amantadine, dextromethorphan) or dopaminergic drugs.[4][3]
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.
US: Prescription only. UK: Prescription only. DE: Prescription only (Rx)
Interactions & Contraindications
Drug interactions
Other dissociatives (NMDA antagonists) Ketamine, amantadine or dextromethorphan add NMDA-antagonist effects with potential CNS toxicity, so combine only with caution.[4]
Urinary acidifiers or alkalinisers Drugs or diets that alkalinise the urine (sodium bicarbonate, carbonic-anhydrase inhibitors) reduce memantine excretion and raise its levels.[4][3]
Dopaminergic drugs (levodopa, dopamine agonists), Anticholinergic drugs Possible additive effects with dopaminergic agents (levodopa, dopamine agonists) and with anticholinergics.[4]
Contraindications
Known hypersensitivity to the drug known hypersensitivity to memantine.[3]
Kidney or liver impairment severe renal impairment needs dose reduction, and caution is needed with conditions or drugs that raise urine pH.[3][4]
Current or prior seizure disorder history of seizures or epilepsy.[4]
Cardiovascular disease, hypertension or arrhythmia caution in severe cardiovascular disease.[4]
No interactions or contraindications listed.
Usage & Context
- A prescription medicine (Namenda, Axura, Ebixa) for moderate-to-severe Alzheimer's disease, where it modestly slows cognitive and functional decline: often combined with a cholinesterase inhibitor.
- Also used off-label or investigationally for other indications (for example to help prevent cognitive decline after whole-brain radiotherapy) and studied across various neuropsychiatric conditions.
- Rarely used recreationally as a dissociative: its slow onset, very long duration and lack of euphoria make it unattractive and hard to control.
Sources & Evidence
- PubChem: Memantine (CID 4054) — identifiers & computed properties
- IUPHAR/BPS Guide to PHARMACOLOGY: memantine (ligand 4253) — NMDA (GluN2C) antagonist data CC BY-SA 4.0
- FDA: NAMENDA XR (memantine hydrochloride) extended-release capsules — Prescribing Information (indications, dosing, pharmacology)
- Wikipedia: Memantine (pharmacology, pharmacokinetics, medical use, adverse effects & legal status) CC BY-SA 4.0
- Chen HS, Pellegrini JW, Aggarwal SK, et al. (1992). Open-channel block of N-methyl-D-aspartate (NMDA) responses by memantine: therapeutic advantage against NMDA receptor-mediated neurotoxicity. J Neurosci 12:4427-36.
PMID 1432103 · doi:10.1523/JNEUROSCI.12-11-04427.1992
- Xia P, Chen HS, Zhang D, et al. (2010). Memantine preferentially blocks extrasynaptic over synaptic NMDA receptor currents in hippocampal autapses. J Neurosci 30:11246-50.
PMID 20720132 · doi:10.1523/JNEUROSCI.2488-10.2010
- Rammes G, Rupprecht R, Ferrari U, et al. (2001). The N-methyl-D-aspartate receptor channel blockers memantine, MRZ 2/579 and other amino-alkyl-cyclohexanes antagonise 5-HT(3) receptor currents in cultured HEK-293 and N1E-115 cell systems in a non-competitive manner. Neurosci Lett 306:81-4.
PMID 11403963 · doi:10.1016/s0304-3940(01)01872-9
- Aracava Y, Pereira EF, Maelicke A, et al. (2005). Memantine blocks alpha7* nicotinic acetylcholine receptors more potently than n-methyl-D-aspartate receptors in rat hippocampal neurons. J Pharmacol Exp Ther 312:1195-205.
PMID 15522999 · doi:10.1124/jpet.104.077172
- 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
- Temme L, Schepmann D, Schreiber JA, et al. (2018). Comparative Pharmacological Study of Common NMDA Receptor Open Channel Blockers Regarding Their Affinity and Functional Activity toward GluN2A and GluN2B NMDA Receptors. ChemMedChem 13:446-452.
PMID 29377520 · doi:10.1002/cmdc.201700810