2008
Targeting the glutamatergic system to develop novel, improved therapeutics for mood disorders
Sanacora G, Zarate CA, Krystal JH, Manji HK. Targeting the glutamatergic system to develop novel, improved therapeutics for mood disorders. Nature Reviews Drug Discovery 2008, 7: 426-437. PMID: 18425072, PMCID: PMC2715836, DOI: 10.1038/nrd2462.Peer-Reviewed Original ResearchConceptsGlutamatergic systemMood disordersAntidepressant effectsNMDA antagonistsDouble-blind placebo-controlled crossover studyTreatment-resistant major depressive disorderPlacebo-controlled crossover studyGlutamate release inhibitorSignificant antidepressant effectNMDA receptor expressionRecurrent mental illnessSingle intravenous doseMajor depressive disorderPotential novel therapeuticsGlutamatergic abnormalitiesCrossover studyGlutamate releaseIntravenous doseMood stabilizersDepressive disorderReceptor expressionReceptor modulatorsEvidence of alterationsCerebrospinal fluidAMPA potentiators
2001
NMDA receptor regulation of memory and behavior in humans
Newcomer J, Krystal J. NMDA receptor regulation of memory and behavior in humans. Hippocampus 2001, 11: 529-542. PMID: 11732706, DOI: 10.1002/hipo.1069.Peer-Reviewed Original ResearchConceptsNMDA receptor hypofunctionReceptor hypofunctionN-methyl-D-aspartate (NMDA) receptor hypofunctionNMDA receptor antagonist drugsNMDA receptor systemAge-related decreaseNMDA receptor regulationReceptor antagonist drugsClinical syndromeNeuropathological featuresNMDA antagonistsNMDA receptorsNeurotoxic processesAntagonist drugsAdult brainHypofunctionBehavioral dysfunctionHuman studiesRange of effectsReceptor regulationReceptor systemBrain functionBrain ageAdverse effectsDisease conditionsAttenuation of Ketamine Effects by Nimodipine Pretreatment in Recovering Ethanol Dependent Men: Psychopharmacologic Implications of the Interaction of NMDA and L-Type Calcium Channel Antagonists
Krupitsky E, Burakov A, Romanova T, Grinenko N, Grinenko A, Fletcher J, Petrakis I, Krystal J. Attenuation of Ketamine Effects by Nimodipine Pretreatment in Recovering Ethanol Dependent Men: Psychopharmacologic Implications of the Interaction of NMDA and L-Type Calcium Channel Antagonists. Neuropsychopharmacology 2001, 25: 936-947. PMID: 11750186, DOI: 10.1016/s0893-133x(01)00346-3.Peer-Reviewed Original ResearchConceptsVoltage-sensitive calcium channelsL-type voltage-sensitive calcium channelsKetamine effectsStimulant effectsCalcium channelsDouble-blind placebo-controlled studyN-methyl-D-aspartate (NMDA) glutamate receptorsL-type calcium channel antagonistL-type VSCC antagonistBehavioral effectsTransient behavioral effectsPlacebo-controlled studyCalcium channel antagonistsImproved memory functionInteraction of NMDAAspects of schizophreniaNimodipine pretreatmentVSCC antagonistsVerbal fluency impairmentPatient groupKetamine responseChannel antagonistsNMDA antagonistsNMDA receptorsEthanol intoxication
1999
Therapeutic Implications of the Hyperglutamatergic Effects of NMDA Antagonists
Krystal J, Belger A, D'Souza D, Anand A, Charney D, Aghajanian G, Moghaddam B. Therapeutic Implications of the Hyperglutamatergic Effects of NMDA Antagonists. Neuropsychopharmacology 1999, 21: s143-s157. DOI: 10.1016/s0893-133x(99)00102-5.Peer-Reviewed Original ResearchHealthy human subjectsNMDA antagonist effectsNMDA antagonistsClinical studiesMetabotropic glutamate receptor agonistN-methyl-D-aspartate (NMDA) subtypeD2 receptor blockadeGlutamate receptor agonistsD2 receptor stimulationDopamine 2 receptorNovel pharmacologic strategiesEffects of ketaminePathophysiology of schizophreniaCourse of schizophreniaNovel pharmacotherapeutic strategiesHuman subjectsHyperglutamatergic stateSerotonin 2AGlutamate neuronsGlutamate releaseCerebral cortexPharmacologic strategiesCurrent antipsychoticsPharmacotherapeutic strategiesSubanesthetic dosesGlutamate and post-traumatic stress disorder: toward a psychobiology of dissociation.
Chambers RA, Bremner JD, Moghaddam B, Southwick SM, Charney DS, Krystal JH. Glutamate and post-traumatic stress disorder: toward a psychobiology of dissociation. Seminars In Clinical Neuropsychiatry 1999, 4: 274-81. PMID: 10553033, DOI: 10.153/scnp00400274.Peer-Reviewed Original ResearchConceptsPost-traumatic stress disorderGlutamate releaseNMDA antagonistsStress disorderN-methyl-D-aspartate (NMDA) subtypeDevelopment of PTSDDissociative symptomsStress exposureRecent preclinical dataTraumatic stress exposureHyperglutamatergic stateNeuroprotective potentialPreclinical dataNeural toxicityClinical studiesGlutamate receptorsTraumatized individualsPerceptual effectsPerceptual alterationsNeural plasticityAntagonistBrain functionSymptomsInfluence behaviorDrugsNMDA Agonists and Antagonists as Probes of Glutamatergic Dysfunction and Pharmacotherapies in Neuropsychiatric Disorders
Krystal J, D'Souza C, Petrakis I, Belger A, Berman R, Charney D, AbiSaab W, Madonick S. NMDA Agonists and Antagonists as Probes of Glutamatergic Dysfunction and Pharmacotherapies in Neuropsychiatric Disorders. Harvard Review Of Psychiatry 1999, 7: 125-143. PMID: 10483932, DOI: 10.3109/hrp.7.3.125.Peer-Reviewed Original ResearchConceptsN-methyl-D-aspartate (NMDA) subclassChronic pain syndromePain syndromeGlutamatergic dysfunctionNMDA agonistClinical studiesMajor depressionNMDA antagonistsGlutamate receptorsCoagonist siteParkinson's diseaseHuman psychopharmacological studiesPartial agonistAlzheimer's diseaseNeuropsychiatric conditionsNeuropsychiatric disordersDiseasePsychopharmacological studiesAnxiety disordersHuntington's diseaseAgonistsAntagonistTherapeutic hypothesesDisordersAddiction disorders