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psx:substance/memantine/proposal/duration/359fc164-d636-40ec-9254-d117de876d9d

proposal2026-05-09recordapproved

derived from · upstream

none recorded

feeds · downstream

Closure of psx:substance/memantine/proposal/duration/359fc164-d636-40ec-9254-d117de876d9d: 0 upstream, 1 downstream.

psx:substance/memantine/proposal/duration/359fc164-d636-40ec-9254-d117de876d9d
└─ derived_from  value/duration/oral/total@1

indented by distance from this node, not by parentage

1Provenance card

the boundary, as counts

Sources

4124 with DOI

27 strong · 10 moderate · 4 weak

Compilations

22026-05-09T11:13:49.359Z

pipeline-v5 · prompt hash not recorded — run predates 2026-09

Decisions

31last ruled 2026-06-04

0 awaiting a ruling

Issued documents

42026-10-19T20:32:44.706Z

notice · info card · emergency

Searches

200 with no results

queries and counts on the build

Claims checked

6652 supported

52 supported · 14 not

Correspondence

0received

consent field ships in Phase 4

Edges

237

derivations recorded for this entity

Complete over 41 sources, 2 compilations, and 31 decisions.Not here: the private journal (never).Working material — drafts, discards, unsupported claims — is listed below and readable on the working page.Cite: psychedex.org/substances/memantine/archive

2Build

one panel per compilation run

generation run 2026-04-28

10 min failedmodel not recordedplan not recordedrun/14f5ddc7…

research

no artifact

draft

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publish

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Selection

results seen0
selected by the model0
consumed as sources41

Verification

claims checked0
supported0
partially supported0
not supported0
inconclusive0
  • record
  • seen / partial
  • working

The model's own caveats

none raised on this run

Reproduce

inputs
41 source keys (listed under Sources)
plan
not recorded — template version, prompt hash and git SHA are written from 2026-09 onward
model
not recorded
streams
none — agent transcripts are persisted from 2026-09 onward

generation run 2026-05-09

69 min completedmodel pipeline-v5plan not recordedrun/01844f1e…

research

citationsRegistryrecordresearchOutputworking

draft

articleDraftworking

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verificationResultworking

simplify

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publish

runMetarecordrunSummaryrecord

Selection

results seen116
selected by the model45
consumed as sources41

Verification

claims checked66
supported45
partially supported7
not supported0
inconclusive14
  • record
  • seen / partial
  • working

The model's own caveats

1 further caveat recorded as free text — readable on the working page

Reproduce

inputs
41 source keys (listed under Sources)
plan
not recorded — template version, prompt hash and git SHA are written from 2026-09 onward
model
pipeline-v5
streams
none — agent transcripts are persisted from 2026-09 onward
20 searches — query, source, results, what was kept and why
20 searches for this run
#sourcequeryseenkeptrationale
1PubChemmemantine11Only result; confirms chemical identity
2PubMedmemantine sigma-1 receptor agonist neuroprotection32Relevant to sigma-1 pharmacology claim in brief
3OpenAlexmemantine NMDA receptor antagonist102Reisberg is the landmark RCT; Traynelis is the canonical NMDA receptor pharmacology review
4PubMedmemantine pharmacokinetics bioavailability half-life metabolism human22These directly address pharmacokinetics of memantine
5PubMedmemantine NMDA receptor antagonist mechanism pharmacology126Selected papers covering mechanism, novel targets, clinical use, and receptor binding
6PubMedmemantine NMDA receptor channel block kinetics voltage-dependent84These provide binding kinetics and mechanism data
7PubMedmemantine adverse effects safety tolerability clinical study104Clinical safety and tolerability data
8PubMedget_pubmed_article 3089174211Highest quality systematic review
9WebSearchmemantine history 1968 1972 synthesis Merz pharmaceutical first patent aminoadamantane102Historical discovery and approval timeline
10PubMedmemantine depression anxiety OCD PTSD treatment11Psychiatric off-label use coverage
11WebSearchmemantine legal status scheduling USA UK EU Canada Australia controlled substance102Legal status data not available via PubMed
12PubChem + literaturememantine chemical identity verification11Chemical identity verification
13PubMedget_pubmed_article 1267286011Landmark clinical trial
14WebFetchHAL netnographic analysis memantine misuse11Primary source for recreational use patterns
15ClinicalTrials.govmemantine155Broad range of clinical trial contexts
16WebFetchStatPearls memantine pharmacokinetics drug interactions adverse effects11Most complete pharmacokinetic and safety summary
17WebSearchmemantine recreational use dissociative effects subjective experience Erowid Reddit102Subjective/recreational use data not in academic databases
18PubMedmemantine overdose toxicity case report11Only published overdose case report found
19WebSearchmemantine pharmacokinetics bioavailability 100% half-life 60-80 hours protein binding 45% renal excretion102Verified pharmacokinetic parameters
20PubMedmemantine NMDA receptor channel block kinetics voltage-dependent84Primary receptor pharmacology data
66 claims by section — every cited sentence, checked against its source
safety13 · 8 ok

  • Claim in safety — inconclusiveinconclusiveworking →

  • In the pivotal 28-week RCT (n=252), premature discontinuation due to adverse events was no greater with memantine than placebosupported

    Landmark RCT (n=252) showing memantine 20mg/day superior to placebo...well tolerated nejmoa013128

  • The sole published overdose case report (Cekmen et al., 2011) documents a 35-year-old woman who ingested 2,000 mg (200 x 10 mg tablets, approximately 28 times the maximum therapeutic dose)supported

    Case report: 35-year-old woman ingested 2000mg (200 x 10mg tablets) pmid:21954534

  • The patient made a full recovery following normalization of memantine plasma levels.supported

    Treated with plasmapheresis (6 cycles); full recovery pmid:21954534

  • Claim in safety — inconclusiveinconclusiveworking →

  • Animal studies demonstrated that memantine inhibits morphine withdrawal intensity and blocks acquisition and expression of morphine conditioned place preferencesupported

    Memantine inhibited intensity of morphine withdrawal and acquisition/expression of morphine-induced conditioned place preference pmid:12629525

  • A systematic review of six clinical trials found benefit when memantine (5–60 mg/day) was added to methadone or buprenorphine maintenance but not to naltrexone.supported

    Six trials reviewed; memantine beneficial with methadone or buprenorphine for OUD but not with naltrexone; doses 5-60mg/day j.jsat.2019.10.003

  • Claim in safety — inconclusiveinconclusiveworking →

  • Claim in safety — inconclusiveinconclusiveworking →

  • Claim in safety — inconclusiveinconclusiveworking →

  • Dopaminergic agents (L-DOPA): some enhancement of L-DOPA effects is possible via NMDA–dopamine circuit interaction, historically exploited in Parkinson's disease treatment.supported

    memantine's clinical history in Europe for PD; approval for AD pmid:17678953

  • Sigma-1 agonists: preclinical evidence suggests an antagonistic (not synergistic) interaction with memantine for memory protection in Alzheimer's disease models.supported

    antagonism (CI>1) with memantine in memory protection j.bbr.2015.09.020

  • Memantine should be used with caution in patients with a lowered seizure threshold.supported

    unconscious, nystagmus, GCS 6, tachycardia 130bpm, hypertension 160/90, mydriasis, convulsions pmid:21954534

pharmacology12 · 10 ok

  • Memantine is a moderate-affinity, uncompetitive, voltage-dependent open-channel blocker of N-methyl-D-aspartate (NMDA)-type ionotropic glutamate receptorssupported

    memantine as clinically tolerated uncompetitive open-channel NMDA blocker with rapid off-rate pmid:15974913

  • Memantine is a moderate-affinity, uncompetitive, voltage-dependent open-channel blocker of N-methyl-D-aspartate (NMDA)-type ionotropic glutamate receptorssupported

    IC50 of 1-3 µM at NMDA receptors in vitro pmid:15510240

  • Under pathological conditions — such as the tonic, low-level glutamate elevation associated with excitotoxic neurodegeneration — channels remain open long enough for memantine to enter and block, reducing excessive Ca2+ influx without abolishing physiological signalingsupported

    Reviews the UFO drug concept; memantine as clinically tolerated uncompetitive open-channel NMDA blocker with rapid off-rate pmid:15974913

  • Under pathological conditions — such as the tonic, low-level glutamate elevation associated with excitotoxic neurodegeneration — channels remain open long enough for memantine to enter and block, reducing excessive Ca2+ influx without abolishing physiological signalingsupported

    mechanism of open-channel block with rapid off-rate pmid:15717010

  • Lipton and colleagues formalized this as the uncompetitive/fast off-rate (UFO) drug concept.supported

    UFO drug concept; S-nitrosylation pathway pmid:17678953

  • Claim in pharmacology — inconclusiveinconclusiveworking →

  • Partial untrapping (~20%) further differentiates memantine from high-affinity trapped-channel blockers such as MK-801 and phencyclidine: memantine can exit the channel even when the channel closes, whereas MK-801 and ketamine remain fully trapped.supported

    ~20% partial untrapping. Confirms human receptor data matches rodent j.neuropharm.2009.01.012

  • It also blocks nicotinic acetylcholine receptors, including the alpha9alpha10 subtype, though with lower potency than the structurally related cyclohexane analog neramexane.supported

    Neramexane and memantine both block alpha9alpha10 nAChRs at micromolar concentrations; neramexane more potent pmid:17466293

  • Claim in pharmacology — inconclusiveinconclusiveworking →

  • The structurally related amantadine has demonstrated sigma-1 affinity at therapeutically relevant concentrations, and the memantine derivative FENM shows synergistic neuroprotection when combined with sigma-1 agonistspartially supported

    sigma-1 receptors, 5-HT3 receptors, nicotinic receptors, NMDARs are primary targets s00702-021-02306-2

  • The structurally related amantadine has demonstrated sigma-1 affinity at therapeutically relevant concentrations, and the memantine derivative FENM shows synergistic neuroprotection when combined with sigma-1 agonistssupported

    Memantine derivative FENM combined with sigma-1 receptor agonists shows synergistic protection in AD model j.neuropharm.2023.109733

  • However, memantine itself shows an antagonistic interaction (combination index >1) with sigma-1 agonists for memory protection in Alzheimer's disease models, which is inconsistent with sigma-1 agonismsupported

    Sigma-1 agonists show synergy with donepezil but antagonism (CI>1) with memantine in memory protection j.bbr.2015.09.020

summary9 · 8 ok

  • First synthesized by Eli Lilly around 1963–1966 as a candidate antidiabetic agent, memantine's CNS activity was identified by Merz (Frankfurt) and the compound launched in Germany in 1989 for dementia and parkinsonism — years before its NMDA receptor mechanism was fully characterizedpartially supported

    Historical overview: launched in Germany by Merz in 1989 for dementia pmid:12090556

  • FDA approval followed in October 2003supported

    EU approval 2002, US approval October 2003 pmid:15510240

  • Beyond dementia, active clinical investigation spans obsessive-compulsive disorder, PTSD, autism spectrum disorder, opioid use disorder, and chemotherapy-related cognitive decline.partially supported

    Review of memantine in non-dementia psychiatric disorders; evidence for OCD, PTSD holds promise 11634390-000000000-00000

  • Beyond dementia, active clinical investigation spans obsessive-compulsive disorder, PTSD, autism spectrum disorder, opioid use disorder, and chemotherapy-related cognitive decline.supported

    RCT of memantine for social impairment in ASD youth; glutamate levels in pgACC studied as biomarker jamanetworkopen.2025.34927

  • Memantine blocks the NMDA receptor ion channel pore at a site overlapping the Mg²⁺ binding site, with an IC₅₀ of 0.79 ± 0.02 μM at −70 mV at human GluN1/GluN2A receptorssupported

    Memantine IC50=0.79 µM at human GluN1/GluN2A receptors at -70mV; strong voltage dependency (delta=0.90) j.neuropharm.2009.01.012

  • Its clinical tolerability rests on rapid offset kinetics and partial untrapping (~20%), permitting normal synaptic transmission while preferentially blocking pathologically sustained channel openings — the basis of the uncompetitive/fast off-rate (UFO) drug conceptsupported

    UFO drug concept; S-nitrosylation pathway; memantine's clinical history in Europe for PD; approval for AD pmid:17678953

  • Claim in summary — inconclusiveinconclusiveworking →

  • At therapeutic doses (5–20 mg/day), memantine demonstrates an excellent safety profile with adverse event rates comparable to placebo in 28-week trialssupported

    Landmark RCT (n=252) showing memantine 20mg/day superior to placebo...well tolerated nejmoa013128

  • The exact toxic dose in humans has not been established; the sole published overdose case (2,000 mg) resulted in full recovery following plasmapheresissupported

    35-year-old woman ingested 2000mg (200 x 10mg tablets)...Treated with plasmapheresis (6 cycles); full recovery pmid:21954534

clinical-evidence8 · 6 ok

  • Claim in clinical-evidence — inconclusiveinconclusiveworking →

  • Animal studies demonstrated that memantine inhibits morphine withdrawal intensity and acquisition/expression of morphine conditioned place preference.supported

    Memantine inhibited intensity of morphine withdrawal and acquisition/expression of morphine-induced conditioned place preference pmid:12629525

  • Premature discontinuation due to adverse events was no greater with memantine than placebo.supported

    well tolerated nejmoa013128

  • Claim in clinical-evidence — inconclusiveinconclusiveworking →

  • A systematic review by Sani et al. (2012) evaluated memantine across psychiatric disorders beyond dementia:supported

    Review of memantine in non-dementia psychiatric disorders; evidence for OCD, PTSD holds promise 11634390-000000000-00000

  • Down syndrome: A Phase 2 RCT (Costa et al., 2022) examined memantine for cognitive and adaptive outcomes in adolescents and young adults with Down syndrome. The trial did not meet its primary endpoint.supported

    Phase 2 RCT; memantine did not improve primary episodic memory endpoint in Down syndrome adolescents/young adults; safety profile acceptable s1474-4422(21)00369-0

  • Benefit was observed in combination with methadone or buprenorphine maintenance but not with naltrexonesupported

    memantine beneficial with methadone or buprenorphine for OUD but not with naltrexone j.jsat.2019.10.003

  • HIV-associated dementia and neuropathic pain: Clinical trials noted in literature but results not retrieved in this search.supported

    trials for depression, glaucoma, neuropathic pain pmid:15974913

history7 · 6 ok

  • The approval was supported by the pivotal Reisberg et al. trial demonstrating functional and cognitive benefits at 20 mg/day over 28 weeks.supported

    Landmark RCT (n=252) showing memantine 20mg/day superior to placebo on CIBIC-Plus, ADCS-ADLsev, and Severe Impairment Battery in moderate-to-severe AD nejmoa013128

  • Merz launched memantine in Germany in 1989 under the trade names Akatinol and Axura, initially indicated for dementia and parkinsonismpartially supported

    Historical overview: launched in Germany by Merz in 1989 for dementia pmid:12090556

  • Danysz, Parsons, Kornhuber, and colleagues characterized both amantadine and memantine as NMDA receptor antagonists in 1997, demonstrating antiparkinsonian activity in preclinical models and establishing that NMDA receptor antagonism was likely the sole mechanism underlying memantine's antiparkinsonian effects — unlike amantadine, which acts through additional pathwayssupported

    Compares amantadine and memantine as NMDA receptor antagonists; antiparkinsonian activity; NMDA antagonism primary mechanism for memantine pmid:9195603

  • The Lipton group subsequently articulated the mechanistic basis for memantine's clinical tolerability: low-affinity, uncompetitive open-channel block with fast offset kinetics, permitting blockade of pathological tonic activation while sparing normal phasic synaptic transmission.supported

    Explains why high-affinity NMDA antagonists failed clinical trials while memantine succeeded; mechanism of open-channel block with rapid off-rate pmid:15717010

  • US FDA approval followed on 17 October 2003 (NDA 21-627), with Forest Laboratories marketing the compound as Namenda for moderate-to-severe Alzheimer's diseasesupported

    EU approval 2002, US approval October 2003; clinical trials in AD as monotherapy and with donepezil pmid:15510240

  • Active clinical investigation spans psychiatric disorders including obsessive-compulsive disorder, PTSD, bipolar disorder, and autism spectrum disorder, as well as opioid use disorder (as an adjunct to methadone or buprenorphine maintenance)partially supported

    Review of memantine in non-dementia psychiatric disorders; evidence for OCD, PTSD holds promise; bipolar disorder add-on shows antimanic effects 11634390-000000000-00000

  • Claim in history — inconclusiveinconclusiveworking →

neuroscience6 · 6 ok

  • Noorman et al. (2025) showed that memantine enhanced decoding of complex perceptual stimuli reliant on feedback processing (Kanizsa illusory contour integration) but did not affect the decoding of stimuli processed via feedforward pathways — and critically, this modulation occurred exclusively when stimuli were consciously attendedsupported

    memantine selectively enhanced decoding of Kanizsa illusion (feedback/recurrent processing); effect only when stimulus was attended elife.100530

  • A follow-up study confirmed that memantine does not modulate effects of expectation or top-down attention per se, but specifically targets NMDA-dependent recurrent amplification.supported

    memantine did not modulate expectation or attention effects jneurosci.0674-25.2026

  • Proteomic analysis of human hippocampal tissue from memantine-treated Alzheimer's disease patients revealed upregulation of both glutamatergic and GABAergic synaptic pathwayssupported

    Post-mortem proteomics: memantine upregulates postsynaptic glutamatergic and GABAergic receptors in AD hippocampus pmic.70006

  • Memantine's clinical rationale is directly derived from this framework: its uncompetitive, fast off-rate kinetics allow it to attenuate excitotoxic signaling without disrupting the phasic NMDA activation required for synaptic plasticity and memorysupported

    UFO drug concept; S-nitrosylation pathway; memantine's clinical history in Europe for PD; approval for AD pmid:17678953

  • The failure of high-affinity NMDA antagonists (MK-801, PCP-site antagonists, competitive antagonists) in clinical trials — due to psychotomimetic effects and neurotoxicity — underscored that how a drug blocks the NMDA receptor matters as much as whether it blocks.supported

    Explains why high-affinity NMDA antagonists failed clinical trials while memantine succeeded pmid:15717010

  • Does chronic memantine treatment produce lasting synaptic remodeling? The proteomic evidence of glutamatergic and GABAergic pathway upregulation in treated patients suggests adaptive plasticity, but the functional significance of these molecular changes is uncharacterized.supported

    memantine upregulates postsynaptic glutamatergic and GABAergic receptors in AD hippocampus; upregulates mitochondrial proteins pmic.70006

comparative-pharmacology5 · 4 ok

  • Despite similar IC50 values at GluN1/GluN2A receptors (memantine 0.79 uM vs ketamine 0.71 uM at -70 mV), the two compounds diverge substantially in kinetics, trapping behavior, and clinical profile.supported

    Memantine IC50=0.79 µM at human GluN1/GluN2A receptors at -70mV; strong voltage dependency (delta=0.90); rapid double exponential blocking kinetics; ~20% partial untrapping j.neuropharm.2009.01.012

  • Under extreme depolarizing conditions (oxygen-glucose deprivation), ketamine provides greater neuroprotection than memantine, likely due to its full trapping maintaining channel block during sustained depolarization.supported

    ketamine provides greater neuroprotection under extreme depolarizing conditions (OGD) mol.113.089334

  • Both act as NMDA receptor antagonists, but amantadine has additional mechanisms including dopamine reuptake inhibition and sigma-1 receptor activitypartially supported

    sigma-1 receptors, 5-HT3 receptors, nicotinic receptors, NMDARs are primary targets s00702-021-02306-2

  • Claim in comparative-pharmacology — inconclusiveinconclusiveworking →

  • Memantine's partial untrapping and moderate affinity avoid these liabilities, which is why memantine succeeded clinically where earlier NMDA antagonists failed.supported

    Explains why high-affinity NMDA antagonists failed clinical trials while memantine succeeded; mechanism of open-channel block with rapid off-rate pmid:15717010

receptor-pharmacology3 · 2 ok

  • Data from Gilling et al. (2009)supported

    Memantine IC50=0.79 µM at human GluN1/GluN2A receptors at -70mV; strong voltage dependency (delta=0.90); rapid double exponential blocking kinetics; ~20% partial untrapping j.neuropharm.2009.01.012

  • Claim in receptor-pharmacology — inconclusiveinconclusiveworking →

  • 5-HT3 and nAChR data from StatPearls; alpha9alpha10 nAChR data from Plazas et al.supported

    Neramexane and memantine both block alpha9alpha10 nAChRs at micromolar concentrations; neramexane more potent pmid:17466293

chemistry2 · 1 ok

  • Claim in chemistry — inconclusiveinconclusiveworking →

  • The CAS number 19982-08-2 has been confirmed in bioequivalence literature.supported

    Memantine CAS 19982-08-2, 10 mg; long terminal half-life s-0031-1296502

pharmacokinetic-detail1 · 1 ok

  • The long half-life (>60 hours) enables truncated AUC windows (48–72 hours) for bioequivalence assessment.partially supported

    bioequivalence assessment with truncated AUC windows (48-72h) are adequate for drugs with half-lives 24-60h s-0031-1296502

3Sources

41 consumed · sorted by year · feeds = sections resting on it

Sources 1 to 30
yearsourcetierstatusfeeds
2026Alzheimer's disease and memantine effects on NMDA-receptor blockade: non-invasive in vivo insights from magnetoencephalographyLanskey JH, Jafarian A, Hughes LE, et al. · Molecular Psychiatrydoi:10.1038/s41380-025-03288-3strongconsumedcited only
2026Distinct allosteric paths mediate a Ca2+-dependent increase in NMDA receptor sensitivity to open-channel blockersWeaver MG, Abbott JA, Popescu GK · Biophysical Journaldoi:10.1016/j.bpj.2026.02.002strongconsumedcited only
2026Effects on NMDA receptor blockade on feedforward and feedback processingNoorman S, Fahrenfort JJ, Heilbron M, Sergent C, Zantvoord JB, van Gaal S, Stein T · Journal of Neurosciencedoi:10.1523/jneurosci.0674-25.2026strongconsumedcited only
2026Memantine: A look ahead. Insights into structure, syntheses, receptor binding mechanisms, drug hybrids and formulations, and potential repurposingMartínez RF, Sánchez-Gallardo M, Cintas P · European Journal of Medicinal Chemistrydoi:10.1016/j.ejmech.2026.118791strongconsumedcited only
2025A causal role of the NMDA receptor in recurrent processing during perceptual integrationNoorman S, Stein T, Zantvoord J, Fahrenfort J, van Gaal S · eLifedoi:10.7554/elife.100530strongconsumedcited only
2025Memantine Administration Enhances Glutamatergic and GABAergic Pathways in the Human Hippocampus of Alzheimer's Disease PatientsFabrik I, Kupcik R, Fabrikova D, et al. · Proteomicsdoi:10.1002/pmic.70006strongconsumed1 section
2025Memantine inhibits calcium-permeable AMPA receptorsCarrillo E, Montaño Romero A, Gonzalez CU, Turcu AL, Vázquez S, Twomey EC, Jayaraman V · Nature Communicationsdoi:10.1038/s41467-025-60543-5strongconsumed3 sections
2025Memantine to Treat Social Impairment in Youths With Autism Spectrum Disorder: A Randomized Clinical TrialJoshi G, Gönenc A, DiSalvo M, Faraone SV, et al. · JAMA Network Opendoi:10.1001/jamanetworkopen.2025.34927strongconsumed1 section
2024Fluoroethylnormemantine (FENM) shows synergistic protection in combination with a sigma-1 receptor agonist in a mouse model of Alzheimer's diseaseFreyssin A, Carles A, Guehairia S, Rubinstenn G, Maurice T · Neuropharmacologydoi:10.1016/j.neuropharm.2023.109733strongconsumed1 section
2024Memantine - StatPearlsStatPearls contributorsurl:fa77d200ebd27fffweakconsumedcited only
2024Memantine misuse and diversion practices: a netnographic analysis of users' experiences published onlineNot specified · HAL Open Scienceurl:067e5f285b492d58weakconsumedcited only
2023Basic information about memantine and its treatment of Alzheimer's disease and other clinical applicationsPMC contributorsurl:5f1a219836065913weakconsumedcited only
2022Memantine augmentation of sertraline in the treatment of symptoms and executive function among patients with OCDAskari S, Mokhtari S, Shariat SV, et al. · BMC Psychiatrydoi:10.1186/s12888-021-03642-zstrongconsumedcited only
2022Safety, efficacy, and tolerability of memantine for cognitive and adaptive outcome measures in adolescents and young adults with Down syndromeCosta ACS, Brandão AC, Boada R, et al. · The Lancet Neurologydoi:10.1016/s1474-4422(21)00369-0strongconsumedcited only
2021Add-on MEmaNtine to Dopamine Modulation to Improve Negative Symptoms at First Psychosis - NCT04789915Bjorn H. Ebdrupurl:36e6f8444a19102amoderateconsumedcited only
2021Amantadine: reappraisal of the timeless diamond—target updates and novel therapeutic potentialsDanysz W, Dekundy A, Scheschonka A, Riederer P · Journal of Neural Transmissiondoi:10.1007/s00702-021-02306-2strongconsumed2 sections
2020Combination Drug Therapy for the Management of Alzheimer's DiseaseKabir MT, Uddin MS, Mamun AA, et al. · International Journal of Molecular Sciencesdoi:10.3390/ijms21093272strongconsumed1 section
2019Adjunctive memantine for major mental disorders: A systematic review and meta-analysisZheng W, Zhu XM, Zhang QE, et al. · Schizophrenia Researchdoi:10.1016/j.schres.2019.05.019strongconsumed1 section
2019Adjunctive memantine for opioid use disorder treatment: A systematic reviewElias AM, Pepin MJ, Brown JN · Journal of Substance Abuse Treatmentdoi:10.1016/j.jsat.2019.10.003strongconsumed2 sections
2019Memantine for dementiaMcShane R, Westby MJ, Roberts E, Minakaran N, Schneider L, Farrimond LE, Maayan N, Ware J, Debarros J · Cochrane Database of Systematic Reviewsdoi:10.1002/14651858.cd003154.pub6strongconsumedcited only
2019Memantine for prevention of cognitive decline in breast cancer - NCT04033419UNC Lineberger Comprehensive Cancer Centerurl:cde1997bfe9ab8bastrongconsumedcited only
2017Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017Hiemke C, Bergemann N, Clement HW, et al. · Pharmacopsychiatrydoi:10.1055/s-0043-116492moderateconsumed1 section
2016Protection by sigma-1 receptor agonists is synergic with donepezil, but not with memantine, in a mouse model of amyloid-induced memory impairmentsMaurice T · Behavioural Brain Researchdoi:10.1016/j.bbr.2015.09.020strongconsumed2 sections
2013Indistinguishable synaptic pharmacodynamics of the NMDA receptor channel blockers memantine and ketamineEmnett CM, Eisenman LN, Taylor AM, Izumi Y, Zorumski CF, Mennerick S · Molecular Pharmacologydoi:10.1124/mol.113.089334strongconsumed1 section
2012The role of memantine in the treatment of psychiatric disorders other than the dementiasSani G, Serra G, Kotzalidis GD, et al. · CNS Drugsdoi:10.2165/11634390-000000000-00000strongconsumed3 sections
2011A memantin HCL intoxication responsive to plasmapheresis therapyCekmen N, Bedel P, Erdemli O · Bratislavske Lekarske Listypmid:21954534weakconsumed2 sections
2011Memantine for Huntington disease - NCT01458470 clinical trialUniversity of British Columbiaurl:193608e30b09a30fstrongconsumedcited only
2009Potency, voltage-dependency, agonist concentration-dependency, blocking kinetics and partial untrapping of the uncompetitive NMDA channel blocker memantine at human NMDA (GluN1/GluN2A) receptorsGilling KE, Jatzke C, Hechenberger M, Parsons CG · Neuropharmacologydoi:10.1016/j.neuropharm.2009.01.012strongconsumed4 sections
2008Targeting excitotoxic/free radical signaling pathways for therapeutic intervention in glaucomaSeki M, Lipton SA · Progress in Brain Researchdoi:10.1016/s0079-6123(08)01134-5moderateconsumedcited only
2008The use of truncated area under the curves in the bioequivalence evaluation of long half-life drugs: donepezil and memantineErkent U, Koytchev R · Arzneimittel-Forschungdoi:10.1055/s-0031-1296502strongconsumed2 sections
Show all 41 sources — 11 more
Sources 31 to 41
yearsourcetierstatusfeeds
2007Inflammatory mediators leading to protein misfolding and uncompetitive/fast off-rate drug therapy for neurodegenerative disordersLipton SA, Gu Z, Nakamura T · International Review of Neurobiologypmid:17678953moderateconsumed4 sections
2007Inhibition of the alpha9alpha10 nicotinic cholinergic receptor by neramexane, an open channel blocker of NMDA receptorsPlazas PV, Savino J, Kracun S, Gomez-Casati ME, Katz E, Parsons CG, Millar NS, Elgoyhen AB · European Journal of Pharmacologypmid:17466293strongconsumed2 sections
2007Pathologically-activated therapeutics for neuroprotection: mechanism of NMDA receptor block by memantine and S-nitrosylationLipton SA · Current Drug Targetspmid:17504105moderateconsumedcited only
2005The molecular basis of memantine action in Alzheimer's disease and other neurologic disorders: low-affinity, uncompetitive antagonismLipton SA · Current Alzheimer Researchpmid:15974913moderateconsumed2 sections
2004Failures and successes of NMDA receptor antagonists: molecular basis for the use of open-channel blockers like memantineLipton SA · NeuroRxpmid:15717010moderateconsumed4 sections
2004Memantine hydrochloride: pharmacological and clinical profileMöbius HJ, Stöffler A, Graham SM · Drugs of Todaypmid:15510240moderateconsumed3 sections
2003Determinants of trapping block of N-methyl-d-aspartate receptor channelsBolshakov KV, Gmiro VE, Tikhonov DB, Magazanik LG · Journal of Neurochemistrypmid:12969252strongconsumed2 sections
2003Memantine in moderate-to-severe Alzheimer's diseaseReisberg B, Doody R, Stöffler A, Schmitt F, Ferris S, Möbius HJ · New England Journal of Medicinedoi:10.1056/nejmoa013128strongconsumed4 sections
2003Morphine tolerance and reward but not expression of morphine dependence are inhibited by GCPII inhibitor 2-PMPAPopik P, Kozela E, Wróbel M, Wozniak KM, Slusher BS · Neuropsychopharmacologypmid:12629525strongconsumed2 sections
2002Memantine. Merz.Kilpatrick GJ, Tilbrook GS · Current Opinion in Investigational Drugspmid:12090556moderateconsumed2 sections
1997Aminoadamantanes as NMDA receptor antagonists and antiparkinsonian agents--preclinical studiesDanysz W, Parsons CG, Kornhuber J, Schmidt WJ, Quack G · Neuroscience and Biobehavioral Reviewspmid:9195603moderateconsumed3 sections

4Docket

one filing per activity — decisions, correspondence, reports

  1. 0012026-05-09revisionRevision 1

    Initial LLM generation (v5 pipeline, wiki, prose phase)

    psx:substance/memantine/version/1
  2. 0022026-06-04proposal29 value proposals approved together

    one review action inferred from a shared reviewer and instant — the graph records one activity per proposal

    29 items in this filing

    • contraindication · renal
    • contraindication · neurological
    • contraindication · metabolic
    • contraindication · neurological
    • contraindication · cardiovascular
    • contraindication · respiratory
    • dose_tier · threshold
    • dose_tier · light
    • dose_tier · common
    • dose_tier · strong
    • dose_tier · heavy
    • timeline · oral · onset
    • timeline · oral · come_up
    • timeline · oral · peak
    • timeline · oral · plateau
    • timeline · oral · resolution
    • timeline · oral · afterglow
    • toxicity
    • dependence · full
    • withdrawal
    • tolerance
    • dosage · oral
    • duration · oral · onset
    • duration · oral · come_up
    • duration · oral · peak
    • duration · oral · offset
    • duration · oral · total
    • duration · oral · aftereffects
    psx:substance/memantine/proposal/contraindication/9e6c3679-a842-4770-b3d5-f55adc8cca09
  3. 0032026-06-04publicationPublication — backfill
    psx:substance/memantine/pub/f29de86e-8df1-47fb-9413-79153ceb0eac

5Issued documents

what the notice, info card and emergency page said, by hash

Issued documents
documentcontent hashissuedfrom versionsuperseded
info_card9c5b72fe0825fa2c480f481a…2026-10-19 20:32Revision 1current
emergency777b5863d801327b008f5610…2026-09-04 04:30Revision 1current
info_card7261cb28e918d04eddfca56f…2026-09-04 04:30Revision 1superseded2026-10-19
notice2859a8ce709e96c644a50e40…2026-09-04 04:30Revision 1current