2021
Dopamine D1R Receptor Stimulation as a Mechanistic Pro-cognitive Target for Schizophrenia
Abi-Dargham A, Javitch JA, Slifstein M, Anticevic A, Calkins ME, Cho YT, Fonteneau C, Gil R, Girgis R, Gur RE, Gur RC, Grinband J, Kantrowitz J, Kohler C, Krystal J, Murray J, Ranganathan M, Santamauro N, Van Snellenberg J, Tamayo Z, Wolf D, D’Souza D, Srihari V, Gueorguieva R, Patel P, Forselius-Bielen K, Lu J, Butler A, Fram G, Afriyie-Agyemang Y, Selloni A, Cadavid L, Gomez-Luna S, Gupta A, Radhakrishnan R, Rashid A, Aker R, Abrahim P, Nia A, Surti T, Kegeles L, Carlson M, Goldberg T, Gangwisch J, Benedict E, Govil P, Brazis S, Mayer M, de la Garrigue N, Fallon N, Baumvoll T, Abeykoon S, Perlman G, Bobchin K, Elliott M, Schmidt L, Rush S, Port A, Heffernan Z, Laney N, Kantor J, Hohing T, Gray D, Lieberman J. Dopamine D1R Receptor Stimulation as a Mechanistic Pro-cognitive Target for Schizophrenia. Schizophrenia Bulletin 2021, 48: 199-210. PMID: 34423843, PMCID: PMC8781338, DOI: 10.1093/schbul/sbab095.Peer-Reviewed Original ResearchConceptsCortical dopamine neurotransmissionPositive allosteric modulationImportant therapeutic targetPF-06412562Dopaminergic receptorsD1R stimulationDA levelsTolerable dosesLevel of stimulationDopamine neurotransmissionReceptor stimulationTherapeutic targetPartial agonistCognitive deficitsBiased agonismFull agonismTarget engagementAllosteric modulationNew drugsStimulationPoor bioavailabilitySchizophreniaOptimal stimulationDrugsExpression levels
2010
The interplay of cannabinoid and NMDA glutamate receptor systems in humans: Preliminary evidence of interactive effects of cannabidiol and ketamine in healthy human subjects
Hallak JE, Dursun SM, Bosi DC, de Macedo LR, Machado-de-Sousa JP, Abrão J, Crippa JA, McGuire P, Krystal JH, Baker GB, Zuardi AW. The interplay of cannabinoid and NMDA glutamate receptor systems in humans: Preliminary evidence of interactive effects of cannabidiol and ketamine in healthy human subjects. Progress In Neuro-Psychopharmacology And Biological Psychiatry 2010, 35: 198-202. PMID: 21062637, DOI: 10.1016/j.pnpbp.2010.11.002.Peer-Reviewed Original ResearchConceptsBrief Psychiatric Rating ScaleHealthy human subjectsGlutamate receptor systemMale healthy volunteersNMDA receptor antagonistEffects of ketamineTreatment of schizophreniaPsychiatric Rating ScaleHuman subjectsWeak partial agonistNon-significant trendKetamine administrationReceptor antagonistEndocannabinoid systemHealthy volunteersPartial agonistActivation subscalePsychiatric conditionsKetamineRandomized orderReceptor systemBehavioral effectsRating ScaleCannabidiolPreliminary evidence
1999
NMDA 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
1994
Specificity of Ethanollike Effects Elicited by Serotonergic and Noradrenergic Mechanisms
Krystal JH, Webb E, Cooney N, Kranzler HR, Charney DS. Specificity of Ethanollike Effects Elicited by Serotonergic and Noradrenergic Mechanisms. JAMA Psychiatry 1994, 51: 898-911. PMID: 7944878, DOI: 10.1001/archpsyc.1994.03950110058008.Peer-Reviewed Original ResearchConceptsVisual analog scaleAnalog scaleScale scoreVisual analog scale scoreYohimbine hydrochlorideAnalog scale scoreDouble-blind conditionsEffect of mCPPReceptor partial agonistEffects of ethanolNoradrenergic mechanismsIntravenous infusionPlasma levelsSerotonergic systemNoradrenergic systemPlaceboDiscriminative propertiesMale inpatientsYohimbinePlasma prolactinCortisol levelsPartial agonistSerotonergic contributionAlcohol dependenceDays of testing