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
2018
The dose-dependent psychomotor effects of intravenous delta-9-tetrahydrocannabinol (Δ9-THC) in humans
Boggs DL, Cortes-Briones JA, Surti T, Luddy C, Ranganathan M, Cahill JD, Sewell AR, D’Souza D, Skosnik PD. The dose-dependent psychomotor effects of intravenous delta-9-tetrahydrocannabinol (Δ9-THC) in humans. Journal Of Psychopharmacology 2018, 32: 1308-1318. PMID: 30255720, DOI: 10.1177/0269881118799953.Peer-Reviewed Original ResearchConceptsFine motor controlPsychomotor effectsMotor functionPsychomotor functionCannabinoid receptor type 1Motor controlGross motor functionDose-related effectsObserved dose-dependent increaseDose-dependent increaseDose-dependent deficitsMotor timingReceptor type 1Gross motor performancePotential neural mechanismsCambridge Neuropsychological TestMotor deficitsBasal gangliaBlood levelsMotor impairmentDrug conditionsPartial agonistGrooved Pegboard taskSustained attentionType 1
2016
Preferential binding to dopamine D3 over D2 receptors by cariprazine in patients with schizophrenia using PET with the D3/D2 receptor ligand [11C]-(+)-PHNO
Girgis RR, Slifstein M, D’Souza D, Lee Y, Periclou A, Ghahramani P, Laszlovszky I, Durgam S, Adham N, Nabulsi N, Huang Y, Carson RE, Kiss B, Kapás M, Abi-Dargham A, Rakhit A. Preferential binding to dopamine D3 over D2 receptors by cariprazine in patients with schizophrenia using PET with the D3/D2 receptor ligand [11C]-(+)-PHNO. Psychopharmacology 2016, 233: 3503-3512. PMID: 27525990, PMCID: PMC5035321, DOI: 10.1007/s00213-016-4382-y.Peer-Reviewed Original ResearchConceptsDopamine D3 receptorD2 receptorsD3 receptorsReceptor occupancyPartial agonistPositive symptomsD2 receptor partial agonistNegative symptomsPositron emission tomography scanDose-occupancy relationshipD2 receptor occupancyWeeks of dosingEmission tomography scanWeeks of treatmentExposure-response analysisReceptor partial agonistCerebrospinal fluid samplesDopamine D2 receptorsReward-related behaviorsD2 receptor ligandsTomography scanD2 antagonismPatientsDay 1Low doses
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