2023
Restorative effect of NitroSynapsin on synaptic plasticity in an animal model of depression
Tse W, Pochwat B, Szewczyk B, Misztak P, Bobula B, Tokarski K, Worch R, Czarnota-Bojarska M, Lipton S, Zaręba-Kozioł M, Bijata M, Wlodarczyk J. Restorative effect of NitroSynapsin on synaptic plasticity in an animal model of depression. Neuropharmacology 2023, 241: 109729. PMID: 37797736, DOI: 10.1016/j.neuropharm.2023.109729.Peer-Reviewed Original ResearchConceptsMedial prefrontal cortexLong-term potentiationChronic restraint stress mouse modelSynaptic plasticityN-methyl-D-aspartate receptor antagonistRestraint stress mouse modelMale C57BL/6J miceAntidepressant-like activityTail suspension testStress mouse modelFunctional synaptic plasticityMajor depressive disorderAntidepressant potentialPharmacological treatmentPsychotomimetic effectsReceptor antagonistC57BL/6J miceDepressive behaviorSucrose preferenceDepressive disorderNitroSynapsinMouse modelSuspension testBehavioral disturbancesCerebrocortical neurons
2022
Ketamine use in pediatric depression: A systematic review
Meshkat S, Rosenblat J, Ho R, Rhee T, Cao B, Ceban F, Danayan K, Chisamore N, Vincenzo J, McIntyre R. Ketamine use in pediatric depression: A systematic review. Psychiatry Research 2022, 317: 114911. PMID: 37732856, DOI: 10.1016/j.psychres.2022.114911.Peer-Reviewed Original ResearchConceptsSafety of ketamineRandomized clinical trialsPediatric depressionIntravenous ketamineNon-competitive N-methyl-D-aspartate (NMDA) receptor antagonistN-methyl-D-aspartate receptor antagonistSystematic reviewOpen-label trialSevere adverse eventsCommon psychiatric disordersDifferent administration modalitiesAdverse eventsAntidepressant effectsSignificant morbidityMean ageCase reportReceptor antagonistClinical trialsAdministration modalitiesDepressive symptomsPsychiatric disordersKetamine useElectronic databasesLarger sample sizeKetamineKetamine in the Treatment of Obsessive-Compulsive Disorder: A Systematic Review
Bandeira ID, Lins-Silva DH, Cavenaghi VB, Dorea-Bandeira I, Faria-Guimarães D, Barouh JL, Jesus-Nunes AP, Beanes G, Souza LS, Leal GC, Sanacora G, Miguel EC, Sampaio AS, Quarantini LC. Ketamine in the Treatment of Obsessive-Compulsive Disorder: A Systematic Review. Harvard Review Of Psychiatry 2022, 30: 135-145. PMID: 35267254, DOI: 10.1097/hrp.0000000000000330.Peer-Reviewed Original ResearchConceptsObsessive-compulsive disorderSystematic reviewN-methyl-D-aspartate receptor antagonistAppropriate washout periodOpen-label trialPlacebo-controlled trialFirst-line treatmentRetrospective chart reviewUse of ketamineEffects of ketamineMeta-analysis protocolCombination of ketaminePubMed/MEDLINEPreferred Reporting ItemsMore effective treatmentsPotent N-methyl-d-aspartate receptor antagonistKetamine treatmentChart reviewGlutamate modulatorsGood tolerabilityReuptake inhibitorsWashout periodCase reportGlutamatergic neurotransmissionReceptor antagonist
2021
Practice Patterns Related to Mitigation of Neurocognitive Decline in Patients Receiving Whole-Brain Radiation Therapy
Jairam V, Park H, Yu J, Bindra R, Contessa J, Jethwa K. Practice Patterns Related to Mitigation of Neurocognitive Decline in Patients Receiving Whole-Brain Radiation Therapy. International Journal Of Radiation Oncology • Biology • Physics 2021, 111: e569. DOI: 10.1016/j.ijrobp.2021.07.1536.Peer-Reviewed Original ResearchWhole-brain radiation therapyWhole brain radiotherapyRadiation oncologistsPractice patternsBrain radiotherapyWBRT patientsNeurocognitive declineRadiation therapyCommon reasonCurrent evidenceHippocampal-avoidance whole-brain radiotherapyN-methyl-D-aspartate receptor antagonistConventional whole brain radiotherapyBrain radiation therapyNational practice patternsDeleterious cognitive effectsRoutine clinical practiceT-testMATERIAL/METHODSStudent's t-testMost radiation oncologistsIntracranial controlNeurocognitive preservationBrain metastasesMedication costsA systematic review of ketamine for the treatment of depression among older adults
Farheen S, Gupta A, Dhar R, Patadia P, Funaro M, Bhattacharya G, Tampi R. A systematic review of ketamine for the treatment of depression among older adults. American Journal Of Geriatric Psychiatry 2021, 29: s93-s96. DOI: 10.1016/j.jagp.2021.01.089.Peer-Reviewed Educational MaterialsPrimary outcome measureUse of ketamineLate-life depressionTreatment of depressionOlder adultsElectroconvulsive therapyReceptor antagonistLife depressionOutcome measuresCurrent evidenceDepressive symptomsOlder subjectsHamilton Depression Rating Scale scoresN-methyl-D-aspartate receptor antagonistSystematic reviewStudy participantsDepression Rating Scale scoresAdverse effectsBenefits of ketamineTolerability of ketamineCognitive adverse effectsCochrane Central RegisterTreatment-resistant depressionAnti-depressant effectsRelapse of symptoms
2020
Medial PFC AMPA receptor and BDNF signaling are required for the rapid and sustained antidepressant-like effects of 5-HT1A receptor stimulation
Fukumoto K, Fogaça M, Liu RJ, Duman CH, Li XY, Chaki S, Duman RS. Medial PFC AMPA receptor and BDNF signaling are required for the rapid and sustained antidepressant-like effects of 5-HT1A receptor stimulation. Neuropsychopharmacology 2020, 45: 1725-1734. PMID: 32396921, PMCID: PMC7419563, DOI: 10.1038/s41386-020-0705-0.Peer-Reviewed Original ResearchConceptsBrain-derived neurotrophic factorAntidepressant-like effectsMajor depressive disorderMedial prefrontal cortexMPFC infusionSelective stimulationReceptor antagonistAMPA receptorsNon-competitive N-methyl-D-aspartate (NMDA) receptor antagonistTreatment of MDDN-methyl-D-aspartate receptor antagonistSynaptic functionAntidepressant-like actionNovelty-suppressed feedingAMPA receptor antagonistGlutamate AMPA receptorsMPFC 5Antidepressant effectsNeurotrophic factorReceptor agonistDepressive disorderSerotonergic systemReceptor stimulationReceptor activationSynaptic proteinsMemantine Protects From Exacerbation of Ischemic Stroke and Blood Brain Barrier Disruption in Mild But Not Severe Hyperhomocysteinemia
Gu S, Sonkar V, Katare P, Kumar R, Kruger W, Arning E, Bottiglieri T, Lentz S, Dayal S. Memantine Protects From Exacerbation of Ischemic Stroke and Blood Brain Barrier Disruption in Mild But Not Severe Hyperhomocysteinemia. Journal Of The American Heart Association 2020, 9: e013368. PMID: 32067580, PMCID: PMC7070222, DOI: 10.1161/jaha.119.013368.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood-Brain BarrierCell DeathCells, CulturedCystathionine beta-SynthaseDisease Models, AnimalDisease ProgressionExcitatory Amino Acid AntagonistsHomocysteineHomocystinuriaHyperhomocysteinemiaInfarction, Middle Cerebral ArteryMemantineMice, KnockoutNeuronsNeuroprotective AgentsReceptors, N-Methyl-D-AspartateSeverity of Illness IndexConceptsN-methyl-D-aspartatePlasma total homocysteineBlood-brain barrier disruptionTotal homocysteineBrain barrier disruptionIschemic strokeN-methyl-D-aspartate receptor antagonismBarrier disruptionCerebrovascular injuryN-methyl-D-aspartate receptor antagonistExpression of NR2B subunitN-methyl-D-aspartate receptor subunitsExpression of N-methyl-D-aspartate receptor subunitsN-methyl-D-aspartate receptor antagonist memantineCystathionine beta-synthaseEffects of memantineCerebral infarct sizeTargeted treatment strategiesAcute ischemic strokeBlood-brain barrierReceptor antagonismNR2B subunitReceptor antagonistSevere elevationHomocysteine levelsKetamine disinhibits dendrites and enhances calcium signals in prefrontal dendritic spines
Ali F, Gerhard DM, Sweasy K, Pothula S, Pittenger C, Duman RS, Kwan AC. Ketamine disinhibits dendrites and enhances calcium signals in prefrontal dendritic spines. Nature Communications 2020, 11: 72. PMID: 31911591, PMCID: PMC6946708, DOI: 10.1038/s41467-019-13809-8.Peer-Reviewed Original ResearchConceptsDendritic spinesN-methyl-D-aspartate receptor antagonistPrefrontal cortexPrefrontal dendritic spinesApical dendritic spinesSomatostatin-expressing (SST) interneuronsCortico-cortical connectivityElevated calcium levelsMedial prefrontal cortexKetamine actsAntidepressant effectsGABAergic neuronsSST interneuronsKetamine actionPyramidal neuronsNMDAR antagonismReceptor antagonistSubanesthetic ketamineSubanesthetic doseDendritic inhibitionAwake miceCortical interneuronsSynaptic inputsCalcium levelsCalcium transients
2018
The effects of ketamine on prefrontal glutamate neurotransmission in healthy and depressed subjects
Abdallah CG, De Feyter HM, Averill LA, Jiang L, Averill CL, Chowdhury GMI, Purohit P, de Graaf RA, Esterlis I, Juchem C, Pittman BP, Krystal JH, Rothman DL, Sanacora G, Mason GF. The effects of ketamine on prefrontal glutamate neurotransmission in healthy and depressed subjects. Neuropsychopharmacology 2018, 43: 2154-2160. PMID: 29977074, PMCID: PMC6098048, DOI: 10.1038/s41386-018-0136-3.Peer-Reviewed Original ResearchConceptsGlutamate-glutamine cyclingGlutamate neurotransmissionAntidepressant effectsKetamine effectsRodent studiesN-methyl-D-aspartate receptor antagonistRapid antidepressant effectsClinician-Administered Dissociative States ScaleEffects of ketamineGlutamine enrichmentKetamine infusionGlutamate releaseKetamine administrationSubanesthetic dosesPsychotomimetic effectsReceptor antagonistNormal salineSchizophrenia pathophysiologyFrontal cortexMRS scansDepressed subjectsKetamineNeurotransmissionPrefrontal cortexPilot study
2017
Augmentation of Anticancer Drug Efficacy in Murine Hepatocellular Carcinoma Cells by a Peripherally Acting Competitive N‑Methyl‑d‑aspartate (NMDA) Receptor Antagonist
Gynther M, Silvestri I, Hansen J, Hansen K, Malm T, Ishchenko Y, Larsen Y, Han L, Kayser S, Auriola S, Petsalo A, Nielsen B, Pickering D, Bunch L. Augmentation of Anticancer Drug Efficacy in Murine Hepatocellular Carcinoma Cells by a Peripherally Acting Competitive N‑Methyl‑d‑aspartate (NMDA) Receptor Antagonist. Journal Of Medicinal Chemistry 2017, 60: 9885-9904. PMID: 29205034, PMCID: PMC5788303, DOI: 10.1021/acs.jmedchem.7b01624.Peer-Reviewed Original ResearchConceptsMurine hepatocellular carcinoma cellsHepatocellular carcinoma cellsN-methyl-D-aspartate receptor antagonistCompetitive N-methyl-D-aspartate (NMDA) receptor antagonistMultidrug resistanceCarcinoma cellsCancer cellsCommon solid tumorsNMDA receptor inhibitionIntrinsic multidrug resistanceReceptor antagonistReceptor inhibitionAnticancer drug efficacyUnderlying biological mechanismsSolid tumorsDrug efficacyReduced expressionCytotoxic actionSorafenibStructure-activity studiesMDR transportersAnticancer drugsBiological mechanismsCellsPromising strategyInteractive effects of an N-methyl-d-aspartate receptor antagonist and a nicotinic acetylcholine receptor agonist on mismatch negativity: Implications for schizophrenia
Hamilton HK, D'Souza DC, Ford JM, Roach BJ, Kort NS, Ahn KH, Bhakta S, Ranganathan M, Mathalon DH. Interactive effects of an N-methyl-d-aspartate receptor antagonist and a nicotinic acetylcholine receptor agonist on mismatch negativity: Implications for schizophrenia. Schizophrenia Research 2017, 191: 87-94. PMID: 28711472, PMCID: PMC5745273, DOI: 10.1016/j.schres.2017.06.040.Peer-Reviewed Original ResearchConceptsNicotinic acetylcholine receptor agonistAcetylcholine receptor agonistReceptor agonistHealthy volunteersN-methyl-D-aspartate receptor antagonistPathophysiology of schizophreniaAuditory processing abnormalitiesProfile of effectsMMN amplitudeNicotine preventsNicotine administrationReceptor hypofunctionNMDAR hypofunctionNMDAR antagonistsReceptor antagonistMismatch negativity (MMN) event-related potential (ERP) componentPresent doseNicotinic agonistsSchizophrenia patientsCigarette useKetamineDeviant typesNeurophysiological effectsSecondary analysisMMN abnormalities
2016
KETAMINE'S MECHANISM OF ACTION: A PATH TO RAPID‐ACTING ANTIDEPRESSANTS
Abdallah CG, Adams TG, Kelmendi B, Esterlis I, Sanacora G, Krystal JH. KETAMINE'S MECHANISM OF ACTION: A PATH TO RAPID‐ACTING ANTIDEPRESSANTS. Depression And Anxiety 2016, 33: 689-697. PMID: 27062302, PMCID: PMC4961540, DOI: 10.1002/da.22501.Peer-Reviewed Original ResearchConceptsMajor depressive disorderAntidepressant effectsKetamine's mechanismN-methyl-D-aspartate receptor antagonistRapid-acting antidepressant effectsPrefrontal cortexSingle subanesthetic doseRapid antidepressant effectsTreatment-resistant depressionFull therapeutic effectEfficacy of ketamineKetamine's antidepressant effectsRapid acting antidepressantsFuture clinical prospectsGlutamate surgeTraditional antidepressantsAntidepressant medicationCascade of eventsReceptor antagonistSubanesthetic doseDepressive disorderClinical dataTherapeutic effectTreatment responseLimited efficacy
2015
Mutation of the Dyslexia-Associated Gene Dcdc2 Enhances Glutamatergic Synaptic Transmission Between Layer 4 Neurons in Mouse Neocortex
Che A, Truong DT, Fitch RH, LoTurco JJ. Mutation of the Dyslexia-Associated Gene Dcdc2 Enhances Glutamatergic Synaptic Transmission Between Layer 4 Neurons in Mouse Neocortex. Cerebral Cortex 2015, 26: 3705-3718. PMID: 26250775, PMCID: PMC5004750, DOI: 10.1093/cercor/bhv168.Peer-Reviewed Original ResearchConceptsN-methyl-D-aspartate receptor antagonistFunctional synaptic circuitryEvoked glutamate releaseGlutamatergic synaptic transmissionLayer 4 neuronsExcitatory transmissionGlutamate releaseThalamocortical connectionsAmbient glutamateMK-801Receptor antagonistAcute applicationProbability of releaseSomatosensory cortexSynaptic circuitryNMDAR activationSynaptic transmissionSynaptic releaseExcitatory connectivityPostsynaptic NMDARsCortical connectivitySomatosensory neocortexMouse neocortexNMDARNeocortexN‐Methyl‐d‐Aspartate Receptor Antagonism has Differential Effects on Alcohol Craving and Drinking in Heavy Drinkers
Krishnan‐Sarin S, O'Malley SS, Franco N, Cavallo DA, Morean M, Shi J, Pittman B, Krystal JH. N‐Methyl‐d‐Aspartate Receptor Antagonism has Differential Effects on Alcohol Craving and Drinking in Heavy Drinkers. Alcohol Clinical And Experimental Research 2015, 39: 300-307. PMID: 25664775, PMCID: PMC4331214, DOI: 10.1111/acer.12619.Peer-Reviewed Original ResearchConceptsAlcohol drinkingFamily historyHeavy drinkersAlcohol cravingN-methyl-D-aspartate receptor antagonistN-methyl-D-aspartate receptor antagonismAlcohol cue-induced cravingEffects of FHHigher baseline levelsPresence of impulsivityAlcohol use disorderCue-induced cravingAlcohol-induced stimulationReceptor antagonismReceptor antagonistPriming doseNMDA receptorsUse disordersMemantineBaseline levelsModulatory influencePotential efficacyAlcohol accessDrinkersEighth day
2013
Two cases of delayed-onset suicidal ideation, dysphoria and anxiety after ketamine infusion in patients with obsessive–compulsive disorder and a history of major depressive disorder
Niciu MJ, Grunschel B, Corlett PR, Pittenger C, Bloch MH. Two cases of delayed-onset suicidal ideation, dysphoria and anxiety after ketamine infusion in patients with obsessive–compulsive disorder and a history of major depressive disorder. Journal Of Psychopharmacology 2013, 27: 651-654. PMID: 23676198, DOI: 10.1177/0269881113486718.Peer-Reviewed Original ResearchConceptsObsessive-compulsive disorderAntidepressant effectsPsychiatric comorbidityComorbid depressionNon-competitive N-methyl-D-aspartate (NMDA) receptor antagonistN-methyl-D-aspartate receptor antagonistTreatment-refractory obsessive-compulsive disorderAcute antidepressant effectsTreatment-resistant unipolarOpen-label trialSevere respiratory depressionAdverse neuropsychiatric effectsComorbid psychiatric disordersMinimal depressive symptomsOff-label useMajor depressive disorderStart of infusionRespiratory depressionIntravenous ketamineNeuropsychiatric effectsKetamine infusionBipolar depressionReceptor antagonistDepressive disorderSedative effects
2012
Capturing the Angel in “Angel Dust”: Twenty Years of Translational Neuroscience Studies of NMDA Receptor Antagonists in Animals and Humans
Moghaddam B, Krystal JH. Capturing the Angel in “Angel Dust”: Twenty Years of Translational Neuroscience Studies of NMDA Receptor Antagonists in Animals and Humans. Schizophrenia Bulletin 2012, 38: 942-949. PMID: 22899397, PMCID: PMC3446228, DOI: 10.1093/schbul/sbs075.Peer-Reviewed Original ResearchMeSH KeywordsAllosteric RegulationAnimalsAntipsychotic AgentsBrief Psychiatric Rating ScaleCerebral CortexDisease Models, AnimalDopamineEmotionsGlutamic AcidHumansKetamineNeurosciencesPhencyclidinePsychoses, Substance-InducedReceptor, Metabotropic Glutamate 5Receptors, Dopamine D2Receptors, Metabotropic GlutamateReceptors, N-Methyl-D-AspartateSchizophreniaSynapsesTranslational Research, BiomedicalConceptsNMDA receptor antagonistReceptor antagonistDopamine hypothesisN-methyl-D-aspartate receptor antagonistGlutamate synaptic functionTranslational neuroscience studiesTreatment of schizophreniaPathophysiology of schizophreniaPotential treatment targetPotential new targetsDopamine antagonistsCortical functionAnimal studiesTreatment targetsClinical testingSynaptic functionAntagonistTranslational toolSchizophreniaTranslational research fundingTranslational researchPotential mechanismsNew targetsAngel dustSystems neuroscience
2011
Glutamatergic Modulation of Auditory Information Processing in the Human Brain
Gunduz-Bruce H, Reinhart RM, Roach BJ, Gueorguieva R, Oliver S, D'Souza DC, Ford JM, Krystal JH, Mathalon DH. Glutamatergic Modulation of Auditory Information Processing in the Human Brain. Biological Psychiatry 2011, 71: 969-977. PMID: 22036036, PMCID: PMC3290754, DOI: 10.1016/j.biopsych.2011.09.031.Peer-Reviewed Original ResearchConceptsN-acetylcysteineAuditory mismatch negativityReceptor antagonistN-methyl-D-aspartate receptor antagonistAspartate glutamate receptor antagonistOral N-acetylcysteinePlacebo-controlled studyGlutamate receptor antagonistsEffects of ketamineInfusion of salineMismatch negativityTest dayMMN amplitudeCystine-glutamate exchangerAuditory information processingP300 event-related potentialGlutamatergic modulationCognitive enhancing agentsEvent-related potentialsKetamine effectsHealthy volunteersHealthy humansSchizophrenia patientsPositive symptomsKetamineGlutamate N-methyl-D-aspartate Receptor Antagonists Rapidly Reverse Behavioral and Synaptic Deficits Caused by Chronic Stress Exposure
Li N, Liu RJ, Dwyer JM, Banasr M, Lee B, Son H, Li XY, Aghajanian G, Duman RS. Glutamate N-methyl-D-aspartate Receptor Antagonists Rapidly Reverse Behavioral and Synaptic Deficits Caused by Chronic Stress Exposure. Biological Psychiatry 2011, 69: 754-761. PMID: 21292242, PMCID: PMC3068225, DOI: 10.1016/j.biopsych.2010.12.015.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBehavior, AnimalBlotting, WesternChoice BehaviorDendritic SpinesElectrophysiologyExcitatory Amino Acid AntagonistsKetamineNeuronsPhenolsPiperidinesPrefrontal CortexRatsRats, Sprague-DawleyReceptors, N-Methyl-D-AspartateSignal TransductionSirolimusStress, PhysiologicalStress, PsychologicalSynapsesSynaptic TransmissionConceptsGlutamate N-methyl-d-aspartate (NMDA) receptor antagonistN-methyl-D-aspartate receptor antagonistNMDA receptor antagonistReceptor antagonistLayer V pyramidal neuronsChronic unpredictable stress modelMammalian targetStress exposureDepressant-like behaviorLong-term stress exposurePathophysiology of depressionRapid antidepressant actionsSelective NMDA receptorChronic stress exposurePrefrontal cortex neuronsAntidepressant actionAcute treatmentChronic administrationSynaptic deficitsPyramidal neuronsSpine densityRo 25Cortex neuronsFunctional deficitsNMDA receptors
2010
Awake Rat Pharmacological Magnetic Resonance Imaging as a Translational Pharmacodynamic Biomarker: Metabotropic Glutamate 2/3 Agonist Modulation of Ketamine-Induced Blood Oxygenation Level Dependence Signals
Chin CL, Upadhyay J, Marek GJ, Baker SJ, Zhang M, Mezler M, Fox GB, Day M. Awake Rat Pharmacological Magnetic Resonance Imaging as a Translational Pharmacodynamic Biomarker: Metabotropic Glutamate 2/3 Agonist Modulation of Ketamine-Induced Blood Oxygenation Level Dependence Signals. Journal Of Pharmacology And Experimental Therapeutics 2010, 336: 709-715. PMID: 21172908, DOI: 10.1124/jpet.110.173880.Peer-Reviewed Original ResearchConceptsPharmacological magnetic resonance imagingMagnetic resonance imagingBrain activationPeriaqueductal grayMetabotropic Glutamate 2/3 Receptor AgonistN-methyl-D-aspartate receptor antagonistResonance imagingBOLD signalEarly clinical trialsNegative BOLD signalsNovel experimental therapeuticsPositive BOLD signalRegion-specific mannerPhMRI studiesReceptor antagonistPharmacodynamic biomarkersReceptor agonistSubanesthetic doseAgonist modulationClinical trialsAwake ratsHippocampal regionBasic research findingsDose selectionAnesthetized animals
2001
Potential and Current Use of N-Methyl-D-Aspartate (NMDA) Receptor Antagonists in Diseases of Aging
Le D, Lipton S. Potential and Current Use of N-Methyl-D-Aspartate (NMDA) Receptor Antagonists in Diseases of Aging. Drugs & Aging 2001, 18: 717-724. PMID: 11735619, DOI: 10.2165/00002512-200118100-00001.Peer-Reviewed Original ResearchConceptsReceptor antagonistN-methyl-D-aspartate receptor antagonistN-methyl-D-aspartate (NMDA) receptor complexSafe NMDA antagonistMultiple clinical trialsNMDA receptor antagonistChronic painClinical trialsNMDA antagonistsGlutamate receptorsParkinson's diseaseNeurological disordersNeurodegenerative diseasesDiseaseAdverse effectsAntagonistReceptor complexCurrent useDrugsAdequate levelPainMemantineDysfunctionNitroglycerinStroke
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