2003
Paradigm shift in neuroprotective drug development: clinically tolerated NMDA receptor inhibition by memantine
Lipton S, Chen H. Paradigm shift in neuroprotective drug development: clinically tolerated NMDA receptor inhibition by memantine. Cell Death & Differentiation 2003, 11: 18-20. PMID: 14647237, DOI: 10.1038/sj.cdd.4401344.Peer-Reviewed Original Research
1999
Neuroprotection by the NMDA receptor-associated open-channel blocker memantine in a photothrombotic model of cerebral focal ischemia in neonatal rat
Stieg P, Sathi S, Warach S, Le D, Lipton S. Neuroprotection by the NMDA receptor-associated open-channel blocker memantine in a photothrombotic model of cerebral focal ischemia in neonatal rat. European Journal Of Pharmacology 1999, 375: 115-120. PMID: 10443569, DOI: 10.1016/s0014-2999(99)00214-9.Peer-Reviewed Original ResearchConceptsMagnetic resonance imagingSide effectsInfarct sizeNeonatal ratsChannel blockersNMDA receptorsFocal cerebral ischemia modelNeurobehavioral side effectsIschemic brain injuryEffects of memantineExcitatory amino acidsInduction of strokeRodent stroke modelsAdult animal modelsCerebral ischemia modelSubstantial side effectsCerebral focal ischemiaNumerous side effectsNeuronal cell culturesNeonatal neuronsPhotochemical thrombosisPhotothrombotic modelNeuronal injuryCerebral ischemiaFocal ischemia
1998
Neuroprotective concentrations of the N-methyl-D-aspartate open-channel blocker memantine are effective without cytoplasmic vacuolation following post-ischemic administration and do not block maze learning or long-term potentiation
Chen H, Wang Y, Rayudu P, Edgecomb P, Neill J, Segal M, Lipton S, Jensen F. Neuroprotective concentrations of the N-methyl-D-aspartate open-channel blocker memantine are effective without cytoplasmic vacuolation following post-ischemic administration and do not block maze learning or long-term potentiation. Neuroscience 1998, 86: 1121-1132. PMID: 9697119, DOI: 10.1016/s0306-4522(98)00163-8.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBody TemperatureBrain IschemiaCytoplasmExcitatory Amino Acid AntagonistsExcitatory Postsynaptic PotentialsIn Vitro TechniquesLong-Term PotentiationMaleMaze LearningMemantineMicroscopy, ElectronNeuronsNeuroprotective AgentsRatsRats, Sprague-DawleyReceptors, N-Methyl-D-AspartateVacuolesConceptsN-methyl-D-aspartate antagonistsLong-term potentiationAspartate antagonistDizocilpine maleateSide effectsUncompetitive N-methyl-D-aspartate antagonistsN-methyl-D-aspartate blockersMorris water maze performancePost-ischemic administrationHypoxia/ischemiaExcitatory postsynaptic currentsN-methyl-D-aspartate (NMDA) channelsAdverse side effectsWater maze performanceHuman CNS disordersExcitotoxic disordersNeuroprotective concentrationsClinical tolerabilityNeuroprotective dosesClinical efficacyInfarct sizePostsynaptic currentsHippocampal slicesCNS disordersAdult rats
1997
Treating AIDS dementia.
Lipton S. Treating AIDS dementia. Science 1997, 276: 1629-30. PMID: 9206820, DOI: 10.1126/science.276.5319.1629b.Peer-Reviewed Original ResearchMechanism of memantine block of NMDA‐activated channels in rat retinal ganglion cells: uncompetitive antagonism.
Chen H, Lipton S. Mechanism of memantine block of NMDA‐activated channels in rat retinal ganglion cells: uncompetitive antagonism. The Journal Of Physiology 1997, 499: 27-46. PMID: 9061638, PMCID: PMC1159335, DOI: 10.1113/jphysiol.1997.sp021909.Peer-Reviewed Original ResearchConceptsRat retinal ganglion cellsRetinal ganglion cellsMicroM memantineGanglion cellsUncompetitive antagonismAction of memantineDegree of blockadeConcentrations of NMDARapid superfusion systemWhole-cell recordingsConcentration of agonistDose-response relationshipLow agonist concentrationsNon-competitive actionDose-response curveOpen channel blockerOpen-channel blockadeMemantine actionEndogenous glutamateMicroM NMDAMemantine concentrationsSuperfusion systemMemantine blockMemantineNMDA
1996
Chronic low-dose glutamate is toxic to retinal ganglion cells. Toxicity blocked by memantine.
Vorwerk C, Lipton S, Zurakowski D, Hyman B, Sabel B, Dreyer E. Chronic low-dose glutamate is toxic to retinal ganglion cells. Toxicity blocked by memantine. Investigative Ophthalmology & Visual Science 1996, 37: 1618-24. PMID: 8675405.Peer-Reviewed Original ResearchConceptsRetinal ganglion cellsLow-dose glutamateGanglion cell survivalGanglion cellsGlutamate toxicityGlutamate levelsMinor elevationsGlutamate concentrationCentral mammalian neuronsEndogenous glutamate levelsCell survivalSuch chronic exposuresGlutamate elevationVitreal glutamateMemantine therapyMemantine treatmentNeuronal lossIntravitreal injectionGlutamate antagonistsMicroM glutamateVehicle injectionChronic elevationMemantineAcute exposureChronic exposure
1993
Delayed administration of memantine prevents N‐methyl‐D‐aspartate receptor‐mediated neurotoxicity
Pellegrini J, Lipton S. Delayed administration of memantine prevents N‐methyl‐D‐aspartate receptor‐mediated neurotoxicity. Annals Of Neurology 1993, 33: 403-407. PMID: 8098195, DOI: 10.1002/ana.410330414.Peer-Reviewed Original ResearchConceptsExcitatory amino acidsN-methyl-D-aspartate receptor-mediated neurotoxicityPotent N-methyl-D-aspartate antagonistNeonatal rat retinal ganglion cellsN-methyl-D-aspartate (NMDA) subtypeN-methyl-D-aspartate antagonistsRat retinal ganglion cellsImmunodeficiency syndrome (AIDS) dementiaAcute neurological conditionsHypoxia/ischemiaChronic neurodegenerative diseasesRetinal ganglion cellsNeuronal cell deathMicroM memantineAntiparkinsonian drugsCentral neuronsGanglion cellsExcessive activationGlutamate receptorsNeurological conditionsNeurodegenerative diseasesHuntington's diseaseNeurotoxicityPrimary culturesDisease
1992
Open-channel block of N-methyl-D-aspartate (NMDA) responses by memantine: therapeutic advantage against NMDA receptor-mediated neurotoxicity
Chen H, Pellegrini J, Aggarwal S, Lei S, Warach S, Jensen F, Lipton. Open-channel block of N-methyl-D-aspartate (NMDA) responses by memantine: therapeutic advantage against NMDA receptor-mediated neurotoxicity. Journal Of Neuroscience 1992, 12: 4427-4436. PMID: 1432103, PMCID: PMC6576016, DOI: 10.1523/jneurosci.12-11-04427.1992.Peer-Reviewed Original ResearchConceptsNMDA receptor-mediated neurotoxicityMK-801Open channel blockTherapeutic advantageLow micromolar concentrationsNMDA open-channel blockersHypoxic-ischemic brain injuryN-methyl-D-aspartate (NMDA) responsesTherapeutic potentialRetinal ganglion cell neuronsRat stroke modelGanglion cell neuronsLevels of glutamateNMDA receptor stimulationCultures of ratConsiderable therapeutic potentialMechanism of actionOpen channel blockerMicromolar concentrationsClinical entityBrain injuryNMDA antagonistsNMDA receptorsExcessive activationStroke modelMemantine prevents HIV coat protein-induced neuronal injury in vitro.
Lipton S. Memantine prevents HIV coat protein-induced neuronal injury in vitro. Neurology 1992, 42: 1403-5. PMID: 1620355, DOI: 10.1212/wnl.42.7.1403.Peer-Reviewed Original ResearchConceptsNeuronal injuryNeuronal damageHIV-1 coat protein gp120Cognitive/motor complexRat retinal ganglion cellsN-methyl-D-aspartate receptorsHuman immunodeficiency virusPossible protective effectNMDA receptor-operated ion channelsRetinal ganglion cellsReceptor-operated ion channelsMicroM memantineNeurologic deficitsImmunodeficiency virusGanglion cellsNMDA antagonistsProtective effectProtein gp120Therapeutic potentialGp120InjuryMemantineMotor complexConcurrent activationIon channels