2010
The use of α-2A adrenergic agonists for the treatment of attention-deficit/hyperactivity disorder
Arnsten A. The use of α-2A adrenergic agonists for the treatment of attention-deficit/hyperactivity disorder. Expert Review Of Neurotherapeutics 2010, 10: 1595-1605. PMID: 20925474, PMCID: PMC3143019, DOI: 10.1586/ern.10.133.Peer-Reviewed Original ResearchMeSH KeywordsAdrenergic alpha-2 Receptor AgonistsAttentionAttention Deficit Disorder with HyperactivityBehaviorCatecholaminesEmotionsHumansPrefrontal CortexReceptors, Adrenergic, alpha-2ConceptsAttention-deficit/hyperactivity disorderPrefrontal cortexHyperactivity disorderPFC functionPFC gray matterPFC pyramidal cellsPyramidal cell networksDorsolateral prefrontal cortexPFC connectionsReceptors inhibitsPyramidal cellsAdrenergic agonistsDendritic spinesVentromedial prefrontal cortexGray matterRelated disordersBrain regionsNeuropsychiatric disordersPotassium channelsDisordersPatientsRecent dataPhysiological connectionTreatmentExecutive functioning
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 stimulationGenetics of Childhood Disorders: XVIII. ADHD, Part 2: Norepinephrine Has a Critical Modulatory Influence on Prefrontal Cortical Function
ARNSTEN A, Lombroso P. Genetics of Childhood Disorders: XVIII. ADHD, Part 2: Norepinephrine Has a Critical Modulatory Influence on Prefrontal Cortical Function. Journal Of The American Academy Of Child & Adolescent Psychiatry 2000, 39: 1201-1203. PMID: 10986819, DOI: 10.1097/00004583-200009000-00022.Peer-Reviewed Original Research
1999
Treatment with the Noradrenergic Alpha-2 Agonist Clonidine, But Not Diazepam, Improves Spatial Working Memory in Normal Young Rhesus Monkeys
Franowicz J, Arnsten A. Treatment with the Noradrenergic Alpha-2 Agonist Clonidine, But Not Diazepam, Improves Spatial Working Memory in Normal Young Rhesus Monkeys. Neuropsychopharmacology 1999, 21: 611-621. PMID: 10516957, DOI: 10.1016/s0893-133x(99)00060-3.Peer-Reviewed Original ResearchMeSH KeywordsAdrenergic alpha-AgonistsAdrenergic alpha-AntagonistsAdrenergic Uptake InhibitorsAnimalsBehavior, AnimalClonidineCognitionDiazepamDose-Response Relationship, DrugFemaleHypnotics and SedativesIdazoxanMacaca mulattaMemoryReaction TimeReceptors, Adrenergic, alpha-2ReserpineSpace PerceptionConceptsAlpha 2 agonist clonidineEffects of clonidineSpatial working memoryChronic reserpine treatmentYoung adult monkeysPrefrontal cortical functionYoung adult humansYoung rhesus monkeysAgonist clonidineReserpine treatmentCortical functionClonidineHuman studiesAdult monkeysHigh dosesLow dosesRhesus monkeysAged monkeysNonhuman primatesDose rangeAdult humansInsufficient dosageConflicting resultsYoung monkeysMonkeys
1997
Catecholamine regulation of the prefrontal cortex
Arnsten A. Catecholamine regulation of the prefrontal cortex. Journal Of Psychopharmacology 1997, 11: 151-162. PMID: 9208378, DOI: 10.1177/026988119701100208.Peer-Reviewed Original ResearchConceptsPrefrontal cortexAdrenergic receptorsAlpha-1 adrenergic receptorsPFC functionPFC cognitive functionAlpha 2A-adrenergic receptorD1 receptor stimulationTreatment of disordersCatecholamine regulationCatecholamine releaseDA stimulationCatecholamine stimulationD2 familyProminent symptomReceptor stimulationModulatory influencePFC dysfunctionCognitive functionSubcortical structuresReview evidenceDetrimental actionsCatecholamines dopamineReceptorsStimulationNorepinephrineNoradrenergic 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
1993
Postsynaptic alpha-2 receptor stimulation improves memory in aged monkeys: Indirect effects of yohimbine versus direct effects of clonidine
Arnsten A, Cai JX. Postsynaptic alpha-2 receptor stimulation improves memory in aged monkeys: Indirect effects of yohimbine versus direct effects of clonidine. Neurobiology Of Aging 1993, 14: 597-603. PMID: 7905189, DOI: 10.1016/0197-4580(93)90044-c.Peer-Reviewed Original ResearchMeSH KeywordsAdrenergic alpha-AntagonistsAgingAnimalsBenzazepinesClonidineCognitionFemaleMacaca mulattaMemoryReceptors, Adrenergic, alpha-2SynapsesYohimbineConceptsPostsynaptic alpha-2 adrenoceptorsPostsynaptic alpha-2 receptorsAlpha-2 adrenoceptorsAlpha 2 receptorsAged monkeysAged animalsAlpha-2 receptor stimulationAlpha-2 adrenergic antagonistBeneficial effectsAlpha-2 antagonistAlpha-2 agonistsCognitive-enhancing effectsNE systemClonidine actsNE releaseAdrenergic antagonistsYohimbine treatmentReceptor stimulationLow dosesClonidineYohimbineNorepinephrineBeneficial dosesYoung monkeysMonkeysCatecholamine mechanisms in age-related cognitive decline
Arnsten A. Catecholamine mechanisms in age-related cognitive decline. Neurobiology Of Aging 1993, 14: 639-641. PMID: 7905190, DOI: 10.1016/0197-4580(93)90054-f.Peer-Reviewed Original ResearchAdrenergic alpha-AgonistsAgingAnimalsCatecholaminesCognitionHaplorhiniHumansReceptors, Adrenergic, alpha-2