2014
A translational investigation targeting stress-reactivity and prefrontal cognitive control with guanfacine for smoking cessation
McKee SA, Potenza MN, Kober H, Sofuoglu M, Arnsten A, Picciotto MR, Weinberger AH, Ashare R, Sinha R. A translational investigation targeting stress-reactivity and prefrontal cognitive control with guanfacine for smoking cessation. Journal Of Psychopharmacology 2014, 29: 300-311. PMID: 25516371, PMCID: PMC4376109, DOI: 10.1177/0269881114562091.Peer-Reviewed Original ResearchConceptsPlacebo-treated subjectsFunctional magnetic resonance imagingCentral noradrenergic pathwaysPrefrontal cognitive dysfunctionSystolic blood pressureClinical outcome dataAd libitum smokingNovel translational approachStress-induced reinstatementMagnetic resonance imagingNicotine-deprived smokersBlood pressureNoradrenergic pathwaysAgonist guanfacineCognitive dysfunctionTreatment periodTobacco cravingQuit attemptsOutcome dataSmokingComplete abstinenceCortisol levelsTranslational investigationsCigarette useGuanfacineGuanfacine extended release for the treatment of attention-deficit/hyperactivity disorder in children and adolescents
Connor DF, Arnsten A, Pearson GS, Greco GF. Guanfacine extended release for the treatment of attention-deficit/hyperactivity disorder in children and adolescents. Expert Opinion On Pharmacotherapy 2014, 15: 1601-1610. PMID: 24992513, DOI: 10.1517/14656566.2014.930437.Peer-Reviewed Original ResearchConceptsAttention-deficit/hyperactivity disorderHyperactivity disorderSymptoms of ADHDEvidence-based treatmentsTraumatic stressBehavioral dysregulationADHD studiesSmall effect sizesPrefrontal cortexAdolescents 6Behavioral conditionsAdolescentsEffect sizeGXRPsycINFO databasesGuanfacinePsychostimulantsShire PharmaceuticalsOpen trialChildrenPotential promiseSecond-line treatmentDisordersAntihypertensive agentsAdrenoreceptor agonist
2012
Guanfacine for the treatment of cognitive disorders: a century of discoveries at Yale.
Arnsten AF, Jin LE. Guanfacine for the treatment of cognitive disorders: a century of discoveries at Yale. The Yale Journal Of Biology And Medicine 2012, 85: 45-58. PMID: 22461743, PMCID: PMC3313539.Peer-Reviewed Original ResearchConceptsAttention deficit hyperactivity disorderPrefrontal cortexCognitive disordersHigher-order cognitive abilitiesDeficit hyperactivity disorderPFC cognitive functionCognitive abilitiesHyperactivity disorderCognitive functionMemory functionPFC functionAgonist guanfacineBrain regionsGuanfacineRecent researchNeurobiologyYale Medical SchoolCentury of discoveryDisordersTherapeutic targetTourette syndromePostsynaptic spinesEmotionsMemorySyndrome
2007
α2A-Adrenoceptors Strengthen Working Memory Networks by Inhibiting cAMP-HCN Channel Signaling in Prefrontal Cortex
Wang M, Ramos BP, Paspalas CD, Shu Y, Simen A, Duque A, Vijayraghavan S, Brennan A, Dudley A, Nou E, Mazer JA, McCormick DA, Arnsten AF. α2A-Adrenoceptors Strengthen Working Memory Networks by Inhibiting cAMP-HCN Channel Signaling in Prefrontal Cortex. Cell 2007, 129: 397-410. PMID: 17448997, DOI: 10.1016/j.cell.2007.03.015.Peer-Reviewed Original ResearchConceptsHCN channel blockadePrefrontal cortical neuronsDelay-related firingΑ2A adrenoceptorsChannel blockadeCortical neuronsInhibition of cAMPAlpha2A adrenoceptorsDendritic spinesNetwork firingElectrophysiological studiesPFC neuronsRecurrent excitationFunctional connectivityHCN channelsPrefrontal cortexHCN1 channelsPFC networksCAMP inhibitionStimulationBlockade
2002
Actions of α-2 noradrenergic agonists on spatial working memory and blood pressure in rhesus monkeys appear to be mediated by the same receptor subtype
Franowicz JS, Arnsten A. Actions of α-2 noradrenergic agonists on spatial working memory and blood pressure in rhesus monkeys appear to be mediated by the same receptor subtype. Psychopharmacology 2002, 162: 304-312. PMID: 12122489, DOI: 10.1007/s00213-002-1110-6.Peer-Reviewed Original ResearchConceptsSame receptor subtypeReceptor subtypesBlood pressureCognitive improvementHypotensive effectNoradrenergic agonistsRhesus monkeysDose-dependent reversalCognitive-enhancing effectsNon-human primatesIdazoxan doseCognitive enhancementMK-912Same dosesHypotensionLow dosesAgonistsSubtypesPotent antagonistAntagonistMK912Recent evidenceClonidineIdazoxanDoses
2000
Noradrenergic alpha-2 receptor agonists reverse working memory deficits induced by the anxiogenic drug, FG7142, in rats
Birnbaum SG, Podell DM, Arnsten A. Noradrenergic alpha-2 receptor agonists reverse working memory deficits induced by the anxiogenic drug, FG7142, in rats. Pharmacology Biochemistry And Behavior 2000, 67: 397-403. PMID: 11164065, DOI: 10.1016/s0091-3057(00)00306-3.Peer-Reviewed Original ResearchConceptsReceptor agonistMemory deficitsAnxiogenic drugsSide effectsAlpha-1 receptor stimulationAlpha-2 adrenoceptor subtypesAlpha-2 receptor agonistCognitive deficitsPrefrontal cortexStress-related neuropsychiatric disordersImidazoline I1 receptor agonistHypotensive side effectsEfficacy of clonidineI1 receptor agonistPrefrontal cognitive deficitsPrefrontal cortical functionClonidine pretreatmentDA turnoverAdrenoceptor agonistsAdrenoceptor subtypesCatecholamine releaseReceptor subtypesCortical functionTherapeutic usefulnessReceptor stimulationThe Alpha-2A-Adrenoceptor Agonist, Guanfacine, Increases Regional Cerebral Blood Flow in Dorsolateral Prefrontal Cortex of Monkeys Performing a Spatial Working Memory Task
Avery R, Franowicz J, Studholme C, van Dyck C, Arnsten A. The Alpha-2A-Adrenoceptor Agonist, Guanfacine, Increases Regional Cerebral Blood Flow in Dorsolateral Prefrontal Cortex of Monkeys Performing a Spatial Working Memory Task. Neuropsychopharmacology 2000, 23: 240-249. PMID: 10942848, DOI: 10.1016/s0893-133x(00)00111-1.Peer-Reviewed Original ResearchMeSH KeywordsAdrenergic alpha-2 Receptor AgonistsAdrenergic alpha-AgonistsAnimalsCerebrovascular CirculationCognitionFemaleGuanfacineImage Processing, Computer-AssistedMacaca mulattaMagnetic Resonance ImagingMemoryPrefrontal CortexSpace PerceptionStimulation, ChemicalTomography, Emission-Computed, Single-PhotonConceptsRegional cerebral blood flowCerebral blood flowPrefrontal cortexDorsolateral prefrontal cortexBlood flowAlpha 2A-adrenoceptorsAuditory association areasSuperior temporal cortexBlood flow tracerSPECT measuresAdrenoceptor agonistsAdrenoceptor stimulationAlpha-2aMemory taskAdrenoreceptor agonistIntravenous cathetersGuanfacine treatmentTemporal cortexRCBF valuesAssociation areasBrain regionsGuanfacineCortexSpatial Working Memory taskCognitive performance
1999
Local infusion of an α-1 adrenergic agonist into the prefrontal cortex impairs spatial working memory performance in monkeys
Mao Z, Arnsten A, Li B. Local infusion of an α-1 adrenergic agonist into the prefrontal cortex impairs spatial working memory performance in monkeys. Biological Psychiatry 1999, 46: 1259-1265. PMID: 10560031, DOI: 10.1016/s0006-3223(99)00139-0.Peer-Reviewed Original ResearchConceptsAlpha-2 adrenoceptorsRat prefrontal cortexPrefrontal cortexAlpha-1 adrenoceptor stimulationAlpha-1 adrenergic agonist phenylephrineAlpha-1 adrenoceptorsAdrenergic agonist phenylephrineDorsolateral prefrontal cortexAgonist phenylephrinePhenylephrine infusionAdrenoceptor stimulationLocal infusionAgonist guanfacineAdrenergic agonistsPrefrontal cortex impairsAdrenoceptorsDelayed-response taskInfusionAlpha 1Rat experimentsStimulationMonkeysGuanfacineSWM functionSWM performance
1998
The α-2a noradrenergic agonist, guanfacine, improves delayed response performance in young adult rhesus monkeys
Franowicz JS, Arnsten A. The α-2a noradrenergic agonist, guanfacine, improves delayed response performance in young adult rhesus monkeys. Psychopharmacology 1998, 136: 8-14. PMID: 9537677, DOI: 10.1007/s002130050533.Peer-Reviewed Original ResearchConceptsYoung adult rhesus monkeysAdult rhesus monkeysHigh dosesDorsolateral prefrontal cortical functionRhesus monkeysDose of idazoxanEffects of guanfacinePrefrontal cortical functionAntagonist idazoxanNoradrenergic agonistsCatecholamine depletionMild sedationAdrenergic agonistsCortical functionDrug effectsAged animalsGuanfacineAdrenergic receptorsLow dosesAged monkeysEffective doseIntact animalsIdazoxanDosesYoung animals
1997
Noradrenergic Influences on Prefrontal Cortical Cognitive Function: Opposing Actions at Postjunctional α1 Versus α2-Adrenergic Receptors
Arnsten A, Steere JC, Jentsch DJ, Li BM. Noradrenergic Influences on Prefrontal Cortical Cognitive Function: Opposing Actions at Postjunctional α1 Versus α2-Adrenergic Receptors. Advances In Pharmacology 1997, 42: 764-767. PMID: 9328010, DOI: 10.1016/s1054-3589(08)60859-5.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsPrefrontal cortexNE releaseΑ2 receptorsCognitive impairmentBeneficial effectsPFC functionBasal NE releasePrefrontal cortical cognitive functionΑ2-adrenergic receptorsCortical cognitive functionsPotential cognitive enhancersAttention deficit hyperactivity disorderMemory functionDeficit hyperactivity disorderPostsynaptic α1Α1d subtypesNE terminalsΑ-adrenoceptorsΑ2 agonistsLithium medicationNoradrenergic influenceOpen trialLithium pretreatmentΑ2A subtypeΑ2A receptors
1995
Guanfacine Treatment of Comorbid Attention-Deficit Hyperactivity Disorder and Tourette's Syndrome: Preliminary Clinical Experience
CHAPPELL P, RIDDLE M, SCAHILL L, LYNCH K, SCHULTZ R, ARNSTEN A, LECKMAN J, COHEN D. Guanfacine Treatment of Comorbid Attention-Deficit Hyperactivity Disorder and Tourette's Syndrome: Preliminary Clinical Experience. Journal Of The American Academy Of Child & Adolescent Psychiatry 1995, 34: 1140-1146. PMID: 7559307, DOI: 10.1097/00004583-199509000-00010.Peer-Reviewed Original ResearchConceptsYale Global Tic Severity ScaleAttention deficit hyperactivity disorderTourette syndromeContinuous Performance TestHyperactivity disorderOpen-label studyCommon side effectsSeverity of motorComorbid attention deficit hyperactivity disorderSafe alternative therapySignificant decreaseTic Severity ScalePreliminary clinical experienceMajority of subjectsConners' Parent Rating ScaleTransient sedationControlled TrialsAlternative therapiesSedative effectsGuanfacine treatmentPhonic ticsSeverity ScaleSide effectsStimulant medicationTic severityAn Open Trial of Guanfacine in the Treatment of Attention-Deficit Hyperactivity Disorder
Hunt R, Arnsten A, Asbell M. An Open Trial of Guanfacine in the Treatment of Attention-Deficit Hyperactivity Disorder. Journal Of The American Academy Of Child & Adolescent Psychiatry 1995, 34: 50-54. PMID: 7860456, DOI: 10.1097/00004583-199501000-00013.Peer-Reviewed Original ResearchConceptsAttention deficit hyperactivity disorderGreater attentional abilityConners' Parent RatingUse of guanfacineAttentional abilitiesConners' hyperactivityParent ratingsHyperactivity disorderFrustration tolerancePatients' mean scoresSelective binding profileHyperactive childrenLonger excretionGuanfacine treatmentADHDHyperactive behaviorMean scoreSide effectsAlpha-2 noradrenergic agonistPsychiatric outpatientsGuanfacineDouble-blind studyBehavioral changesSedative side effectsOpen trial
1991
Behavioral and receptor binding analysis of the α2-adrenergic agonist, 5-bromo-6 [2-imidazoline-2-YL amino] quinoxaline (UK-14304): evidence for cognitive enhancement at an α2-adrenoceptor subtype
Arnsten A, Leslie FM. Behavioral and receptor binding analysis of the α2-adrenergic agonist, 5-bromo-6 [2-imidazoline-2-YL amino] quinoxaline (UK-14304): evidence for cognitive enhancement at an α2-adrenoceptor subtype. Neuropharmacology 1991, 30: 1279-1289. PMID: 1686301, DOI: 10.1016/0028-3908(91)90024-6.Peer-Reviewed Original Research
1988
The alpha-2 adrenergic agonist guanfacine improves memory in aged monkeys without sedative or hypotensive side effects: evidence for alpha-2 receptor subtypes
Arnsten A, Cai J, Goldman-Rakic P. The alpha-2 adrenergic agonist guanfacine improves memory in aged monkeys without sedative or hypotensive side effects: evidence for alpha-2 receptor subtypes. Journal Of Neuroscience 1988, 8: 4287-4298. PMID: 2903226, PMCID: PMC6569464, DOI: 10.1523/jneurosci.08-11-04287.1988.Peer-Reviewed Original ResearchConceptsAlpha-2 receptor subtypesB-HT920Alpha-2 agonistsReceptor subtypesRank order potencyLow dosesDose-response profilesBlood pressureSide effectsHigh dosesAlpha-2 adrenergic agonistsOrder potencyHypotensive side effectsSedative side effectsSubtypes of receptorsAged nonhuman primatesAged rhesus monkeysMemory-enhancing effectsMemory-impairing effectsClonidine effectAgonist guanfacineClonidineAdrenergic agonistsGuanfacineSedation