norepinephrine
DESCRIPTION
neurochemicalTRANSCRIPT
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Norepinephrine
Systematic(IUPAC)name
4[(1R)2amino1hydroxyethyl]benzene1,2diol
Clinicaldata
Tradenames Levarterenol,Levophed,Norepin
AHFS/Drugs.com monograph
Licencedata USFDA:link
Pregnancycategory
AU:B3US:C
Legalstatus AU:PrescriptionOnly(S4)CA:onlyUK:POMUS:only
Routes Intravenous
Pharmacokineticdata
Metabolism Hepatic
Excretion Urine(8496%)
Identifiers
CASnumber 51412
ATCcode C01CA03
PubChem CID439260
DrugBank DB00368
ChemSpider 388394
UNII X4W3ENH1CV
KEGG D00076
ChEBI CHEBI:18357
ChEMBL CHEMBL1437
Synonyms Noradrenaline(R)()Norepinephrinel1(3,4Dihydroxyphenyl)2aminoethanol
NorepinephrineFromWikipedia,thefreeencyclopedia
Norepinephrine(INN)(abbreviatednorepiorNE),alsocallednoradrenaline(BAN)(abbreviatedNA,NAd,ornorad),or4,5trihydroxyphenethylamineisacatecholaminewithmultiplerolesincludingthoseasahormoneandaneurotransmitter.[1]Itisthehormoneandneurotransmittermostresponsibleforvigilantconcentrationincontrasttoitsmostchemicallysimilarhormone,dopamine,whichismostresponsibleforcognitivealertness.[2]
Medicallyitisusedinthosewithseverehypotension.Itdoesthisbyincreasingvasculartone(tensionofvascularsmoothmuscle)throughadrenergicreceptoractivation.
Areasofthebodythatproduceorareaffectedbynorepinephrinearedescribedasnoradrenergic.Thetermsnoradrenaline(fromtheLatin)andnorepinephrine(fromtheGreek)areinterchangeable,withnoradrenalinebeingthecommonnameinmostpartsoftheworld.HowevertheU.S.NationalLibraryofMedicine[3]haspromotednorepinephrineasthefavoredname.ItwasdiscoveredbyUlfvonEulerin1946.[4]
Oneofthemostimportantfunctionsofnorepinephrineisitsroleastheneurotransmitterreleasedfromthesympatheticneuronstoaffecttheheart.Anincreaseinnorepinephrinefromthesympatheticnervoussystemincreasestherateofcontractionsintheheart.[5]Asastresshormone,norepinephrineaffectspartsofthebrain,suchastheamygdala,whereattentionandresponsesarecontrolled.[6]Norepinephrinealsounderliesthefightorflightresponse,alongwithepinephrine,directlyincreasingheartrate,triggeringthereleaseofglucosefromenergystores,andincreasingbloodflowtoskeletalmuscle.Itincreasesthebrain'soxygensupply.[7]
Norepinephrineissynthesizedfromdopaminebydopaminehydroxylaseinthesecretorygranulesofthemedullarychromaffincells.[8]Itisreleasedfromtheadrenalmedullaintothebloodasahormone,andisalsoaneurotransmitterinthecentralnervoussystemandsympatheticnervoussystem,whereitisreleasedfromnoradrenergicneuronsinthelocuscoeruleus.Theactionsofnorepinephrinearecarriedoutviathebindingtoadrenergicreceptors.
Contents
1Medicaluses2Physiologicaleffects
2.1Norepinephrinesystem2.2Roleincognition2.3Fasting2.4Macronutrientintake
3Druginteractions3.1Synthesismodulators3.2Releasemodulators3.3Receptorbindingmodulators3.4Terminationmodulators3.5AlzheimersDisease
4Chemistry5Mechanism
5.1Biosynthesis5.2Vesiculartransport5.3Release5.4Receptorbinding5.5Termination
6Nutritionalsources7Seealso
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Chemicaldata
Formula C8H11NO3
Molecularmass 169.18g/mol
Physicaldata
Density 1.3970.06g/cm3
Meltingpoint 217C(423F)(decomposes)
Boilingpoint 442.6C(828.7F)40.0C
(whatisthis?)(verify)
8References9Externallinks
Medicaluses
Norepinephrineisusedasavasopressormedicationforpatientswithcriticalhypotension.Itisgivenintravenouslyandactsonboth1and2adrenergicreceptorstocausevasoconstriction.Itseffectsareoftenlimitedtotheincreasingofbloodpressurethroughagonistactivityon1and2receptors,andcausingaresultantincreaseinperipheralvascularresistance.Athighdoses,andespeciallywhenitiscombinedwithothervasopressors,itcanleadtolimbischemiaandlimbdeath.Norepinephrineisusedmainlytotreatpatientsinvasodilatoryshockstatessuchassepticshockandneurogenicshock,whileshowingfeweradversesideeffectscomparedtodopaminetreatment.[9]
Physiologicaleffects
Norepinephrineisreleasedwhenahostofphysiologicalchangesareactivatedbyastressfulevent.
Inthebrain,thisiscausedinpartbyactivationofanareaofthebrainstemcalledthelocuscoeruleus(LC).Thisnucleusistheoriginofmostnorepinephrinepathwaysinthebrain.Noradrenergicneuronsprojectbilaterally(sendsignalstobothsidesofthebrain)fromthelocuscoeruleusalongdistinctpathwaystomanylocations,includingthecerebralcortex,limbicsystem,andthespinalcord,forminganeurotransmittersystem.
Norepinephrineisalsoreleasedfrompostganglionicneuronsofthesympatheticnervoussystem,totransmitthefightorflightresponseineachtissue,respectively.Theadrenalmedullacanalsocontributetosuchpostganglionicnervecells,althoughtheyreleasenorepinephrineintotheblood.
Norepinephrinesystem
Thenoradrenergicneuronsinthebrainformaneurotransmittersystem,that,whenactivated,exertseffectsonlargeareasofthebrain.Theeffectsaremanifestedinalertness,arousal,andinfluencesontherewardsystem.
Thenoradrenergicneuronsoriginatebothinthelocuscoeruleusandthelateraltegmentalfield.Theaxonsoftheneuronsinthelocuscoeruleusactonadrenergicreceptorsin:
AmygdalaCingulategyrusCingulumHippocampusHypothalamusNeocortexSpinalcordStriatumThalamusSomeBrainstemnucleiCerebellum
Ontheotherhand,axonsofneuronsofthelateraltegmentalfieldactonadrenergicreceptorsinhypothalamus,forexample.
Thisstructureexplainssomeoftheclinicalusesofnorepinephrine,sinceamodificationofthissystemaffectslargeareasofthebrain.
Roleincognition
Corticalnorepinephrine(NE)releaseduringattentionparadigms(patterns)canincreasethealterationdetectionrate(frequencyatwhichanalterationwasselected)inmultiplecueprobabilitylearningduringtasksinvolvinggivingpredictivecues(suchasauditoryorvisual),andtherebyenhancesubsequentlearning.[10]A.J.Yuetal.developedaBayesianframeworktoexamineNEreleaseininstancesof"unexpecteduncertainty",whereinadrasticalterationinsensoryinformationproducesalargedisparitybetweentopdownexpectationsandwhatactuallyoccurs.[11]ThemodelpredictsthatNElevelsspikewhenthepredictivecontextisswitched,thensubside.Ithasalsobeenshownthatlesionsofthelocuscoeruleusimpairthisattentionalshift.[11]
SMILES
InChI
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Similarly,severalstudieshaveimplicatedtheLCNEsysteminelicitingtheP300,acorticaleventrelatedpotentialthatrespondstoenvironmentalstimuliwithbehaviorallyrelevant,motivational,orattentiongrabbingproperties.[12][13][14][15][16]TheP300mayreflectupdatingofpriorknowledgeregardingstimulirelevantforaccurateandefficientdecisionmaking.SeveralstudieshavesearchedforaP300generatorwithinthebrainandhaveultimatelyconcludedthatthepotentialmusthaveasourcethatisdistributed,synchronousandlocalizedincortex.[17]ThisdefinitionisideallysatisfiedbothfunctionallyandanatomicallybytheLCneuromodulatorysystem.GivenitsbroadprojectionpatternandthecorrelationbetweenNEreleaseandincreasedsensorysignaltransmission,[18]itseemslikelythatnoradrenergiccorticalreleaseistheneuronalmechanismoftheP300.
ExaminationoftheLCstonicfiringpatternhasledtospeculationthatitisimportantfortheexploratorybehavioressentialforlearningrelationsbetweensensoryinput,decisionprocessing,motoroutput,andbehavioralfeedback.[19]Tonicactivationwithintherangeof05Hzhasbeenshowntocorrelatewithlevelsofdrowsiness,accuratetaskperformance,and,whenslightlymoreelevated,distractibilityanderratictaskperformance.Furthermore,phasicactivationoftheLCisobservedinresponsetobothhighlysalient,unconditionedandtaskrelevantstimuli.Thephasicresponseoccursafterstimulationandprecedesabehavioralresponseinatimelockedfashion.[20]Assuch,phasicactivationoftheLCNEsystemisproposedtoenhancesignalprocessingandbehavioralresponsesspecificallytotaskrelevantstimuli.GiventhecontrastingfunctionalrolesofLCtonicandphasicactivity,itisplausiblethatprojectionsfromthisbrainregionareimportantformaintainingabalancebetweenexploratoryandgoaldirectedbehaviorsthatregulateprobabilistic,environmentallearningandcorrespondingdecisionmaking.
TheLCNEsystemreceivesconvergentinputfromtheorbitofrontal(OFC)andanteriorcingulatecortices(ACC).TheOFChasbeenassociatedwithevaluationofreward.Forexample,Tremblayetal.foundthattheresponsemagnitudeofsingleunitsinthisregionisvariedwiththehedonicvalueofastimulus.[21]Additionally,neuronsinthisregionareactivatedbyrewardingstimuli,butnotbyidentificationofthestimulusnorcorrespondingresponsepreparation.ActivationoftheACCappearstoreflectsomeevaluationofcostbenefit.SeveralstudiesshowACCactivationinresponsetoperformanceerror,negativefeedback,ormonetaryloss.[22][23][24]Additionally,ACCrespondstotaskdifficulty.[25]Therefore,ACCactivationmayservetointegrateevaluationsoftaskdifficultywithcorrespondingoutcomeinformationtogaugethebenefitsoftakinganactioninregardstoaparticularenvironmentalstimulus.Conceivably,thefunctionsoftheACCandOFCaredirectlyrelatedtodecisionmaking,andtheirprojectionstoLCmaymodulatethephasicreleaseofNEinordertogainmodulatecorticalresponsestodecisionoutcomes.
LCNEmayplayasignificantroleinsynchronizingcorticalactivityinresponsetoadecisionprocess.Incomputationalmodelingofdecision,themostaccurateandefficientdecisionmechanismsaremathematicallydefinedrandomwalkordriftdiffusionprocessesthatutilizesinglelayerneuralnetworkstocalculatethedisparityinevidencebetweentwooptions.[26]NEreleasegatedbytheLCNEsystemiselicitedafterneuronsprocessingsensoryinformationhavepresumablyreachedadecisionthreshold.[27]Thus,thephasicburstcanalteractivationinallcorticalprocessinglayersinatemporallydependentmanner,essentiallycollapsingthevastinformationprocessingcircuittotheoutcomeofasingledecisionlayer.Brownetal.foundthattheadditionofaphasicLCmechanismwassufficienttoyieldoptimalperformancefromasinglelayerdecisionnetwork.[28]
Fasting
Astudyhasshownthatfastingleadstoincreasedlevelsofnorepinephrine(NE)inthebloodforupto4daysoffasting.[29]
Macronutrientintake
GlucoseintakewasfoundtosignificantlyincreaseplasmaNElevels.Incontrast,proteinandfatintakewasfoundtohavenoeffect.[30]
Druginteractions
Differentmedicationsaffectingnorepinephrinefunctionhavetheirtargetsatdifferentpointsinthemechanism,fromsynthesistosignaltermination.
Synthesismodulators
Methyltyrosineisasubstancethatintervenesinnorepinephrinesynthesisbysubstitutingtyrosinefortyrosinehydroxylase,andblockingthisenzyme.
Vesiculartransportmodulators
Thistransportationcanbeinhibitedbyreserpineandtetrabenazine.[31]
Releasemodulators
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InhibitorsofnorepinephrinereleaseSubstance[32] Receptor[32]
acetylcholine muscarinicreceptornorepinephrine(itself)/epinephrine 2receptor5HT 5HTreceptoradenosine P1receptorPGE EPreceptorhistamine H2receptorenkephalin receptordopamine D2receptorATP P2receptor
Stimulatorsofnorepinephrinerelease
Substance[32] Receptor[32]
epinephrine 2receptorangiotensinII AT1receptor
Receptorbindingmodulators
Examplesincludealphablockersforthereceptors,andbetablockersforthereceptors.
Terminationmodulators
Uptakemodulators
Inhibitors[31]ofuptake1include:
cocainetricyclicantidepressants
desipramineserotoninnorepinephrinereuptakeinhibitorsphenoxybenzamineamphetaminereboxetine
Inhibitors[31]ofuptake2include:
normetanephrinesteroidhormonesphenoxybenzamine
AlzheimersDisease
Thenorepinephrinefromlocusceruleuscellsinadditiontoitsneurotransmitterrolelocallydiffusesfrom"varicosities".Assuch,itprovidesanendogenousantiinflammatoryagentinthemicroenvironmentaroundtheneurons,glialcells,andbloodvesselsintheneocortexandhippocampus.[33]Upto70%ofnorepinephrineprojectingcellsarelostinAlzheimersDisease.IthasbeenshownthatnorepinephrinestimulatesmousemicrogliatosuppressAinducedproductionofcytokinesandtheirphagocytosisofA,suggestingthislossmighthavearoleincausingthisdisease.[33]
Chemistry
Norepinephrineisacatecholamineandaphenethylamine.ThenaturalstereoisomerisL()(R)norepinephrine.Theprefixnorindicatesthatnorepinephrineisthenextlowerhomologofepinephrine.Thetwostructuresdifferonlyinthatepinephrinehasamethylgroupattachedtoitsnitrogen,whereasthemethylgroupisreplacedbyahydrogenatominnorepinephrine.Theprefixnorisderivedasanabbreviationoftheword"normal",usedtoindicateademethylatedcompound.[34][35][36]
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Biosynthesisofnorepinephrine
Mechanism
Norepinephrineissynthesizedfromtyrosineasaprecursor,andpackedintosynapticvesicles.Itperformsitsactionbybeingreleasedintothesynapticcleft,whereitactsonadrenergicreceptors,followedbythesignaltermination,eitherbydegradationofnorepinephrineorbyuptakebysurroundingcells.
Biosynthesis
Norepinephrineissynthesizedbyaseriesofenzymaticstepsintheadrenalmedullaandpostganglionicneuronsofthesympatheticnervoussystemfromtheaminoacidtyrosine.WhiletheconversionstepsofLtyrosinetodopamineoccurspredominantlyinthecytoplasm,theconversionofdopaminetonorepinephrinebydopaminehydroxylaseoccurspredominantlyintheneurotransmittervesicle.
Vesiculartransport
Betweenthedecarboxylationandthefinaloxidation,norepinephrineistransportedintosynapticvesicles.Thisisaccomplishedbyvesicularmonoaminetransporter(VMAT)inthelipidbilayer.Thistransporterhasequalaffinityfornorepinephrine,epinephrineandisoprenaline.[31]
Release
Toperformitsfunctions,norepinephrinemustbereleasedfromsynapticvesicles.Manysubstancesmodulatethisrelease,someinhibitingitandsomestimulatingit.Anactionpotentialreachesthepresynapticmembrane,whichchangesthemembranepolarisation.Calciumionsthusenter,resultinginvesicularfusion,releasingnorepinephrine.
Forinstance,thereareinhibitory2adrenergicreceptorspresynapticallythatgivenegativefeedbackonreleasebyhomotropicmodulation.
Receptorbinding
Norepinephrineperformsitsactionsonthetargetcellbybindingtoandactivatingadrenergicreceptors.Thetargetcellexpressionofdifferenttypesofreceptorsdeterminestheultimatecellulareffect,andthusnorepinephrinehasdifferentactionsondifferentcelltypes.
Termination
Signalterminationisaresultofreuptakeanddegradation.
Uptake
Extracellularuptakeofnorepinephrineintothecytosolisdoneeitherpresynaptically(uptake1)orbynonneuronalcellsinthevicinity(uptake2).Furthermore,thereisavesicularuptakemechanismfromthecytosolintosynapticvesicles.
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Norepinephrinedegradation.Enzymesareshowninboxes.[40]
Comparisonofnorepinephrineuptake
Uptake TransporterVmax(n
mol/g/min)[37]KM[37] Specificity[38] Location Othersubstrates[38] Inhibitors[39]
Uptake1 Norepinephrinetransporter[39]
1.2 0.3norepinephrine>epinephrine>isoprenaline
presynaptic
methylnoradrenaline(nasaldecongestant)tyramineguanethidine
CocaineTricyclicantidepressants(e.g.desipramine)PhenoxybenzamineAmphetamineReboxetine
Uptake2 100 250epinephrine>norepinephrine>isoprenaline
cellmembraneofnonneuronalcells[31]
dopamine5HThistamine
normetanephrinesteroidhormones(e.g.,corticosterone)phenoxybenzamine
Vesicular VMAT[39] [39] ~0.2[39]norepinephrine>epinephrine>isoprenaline[39]
Synapticvesiclemembrane[39]
dopamine[39]
5HT[39]
guanethidine[39]
MPP+[39]
Reserpine[39]
Tetrabenazine
Degradation
Inmammals,norepinephrineisrapidlydegradedtovariousmetabolites.Theprincipalmetabolitesare:
Normetanephrine(viatheenzymecatecholOmethyltransferase,COMT)3,4Dihydroxymandelicacid(viamonoamineoxidase,MAO)Vanillylmandelicacid(3Methoxy4hydroxymandelicacid),alsoreferredtoasvanilmandelateorVMA(viaMAO)3Methoxy4hydroxyphenylethyleneglycol,"MHPG"or"MOPEG"(viaMAO)
Epinephrine(viaPNMT)[41]
Intheperiphery,VMAisthemajormetaboliteofcatecholamines,andisexcretedunconjugatedintheurine.Aminormetabolite(althoughthemajoroneinthecentralnervoussystem)isMHPG,whichispartlyconjugatedtosulfateorglucuronidederivativesandexcretedintheurine.[42]
Nutritionalsources
Thesynthesisofnorepinephrinedependsonthepresenceoftyrosine,anaminoacidfoundinproteinssuchasmeat,nuts,andeggs.Dairyproductssuchascheesealsocontainhighamountsoftyrosine(theaminoacidisnamedfor"tyros",theGreekwordforcheese).However,adulthumansreadilysynthesizetyrosinefromphenylalanine,anessentialaminoacid.Tyrosineistheprecursortodopamine,whichinturnisaprecursortoepinephrineandnorepinephrine.
Seealso
CatecholaminergicpolymorphicventriculartachycardiaHistoryofcatecholamineresearch
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ShownhereisthechemicalstructureofLtyrosine.ThebiosynthesisofnorepinephrinedependsuponthepresenceofLtyrosine,anaminoacidbuildingblockofmanyproteinsinmeat,nuts,andeggs,forexample.
References
1. "Norepinephrinedefinition"(http://dictionary.reference.com/browse/Norepinephrine).dictionary.reference.com.Retrieved24November2008.
2. http://www.medscape.org/viewarticle/523887_43. "RxNorm_full_prescribe_01072013.zip"(http://www.nlm.nih.gov/research/umls/rxnorm/docs/rxnormfiles.html).
U.S.NationalLibraryofMedicine.Retrieved22January2013.4. "Eulernobellecture"(http://www.nobelprize.org/nobel_prizes/medicine/laureates/1970/eulerlecture.pdf).
Retrieved28February2015.5. Guyton,ArthurHall,John(2006)."Chapter10:RhythmicalExcitationoftheHeart".InGruliow,Rebecca.
TextbookofMedicalPhysiology(Book)(11thed.).Philadelphia,Pennsylvania:ElsevierInc.p.122.ISBN0721602401.
6. TanakaM,YoshidaM,EmotoH,IshiiH(September2000)."Noradrenalinesystemsinthehypothalamus,amygdalaandlocuscoeruleusareinvolvedintheprovocationofanxiety:basicstudies".Eur.J.Pharmacol.405(13):397406.doi:10.1016/S00142999(00)005690(https://dx.doi.org/10.1016%2FS00142999%2800%29005690).PMID11033344(https://www.ncbi.nlm.nih.gov/pubmed/11033344).
7. TheHormoneFoundation."TheEndocrineSystem&TypesofHormones."(http://www.hormone.org/endocrine_system.cfm)8. "IntroductiontoAutonomicPharmacology"(http://www.fleshandbones.com/readingroom/pdf/225.pdf)(PDF).ElsevierInternational.Linkredirectedto
commercialsite!9. DeBacker,Danieletal.(4March2010)."ComparisonofDopamineandNorepinephrineintheTreatmentofShock".NewEnglandJournalofMedicine
362(9):11.doi:10.1056/nejmoa0907118(https://dx.doi.org/10.1056%2Fnejmoa0907118).10. DevaugesV,SaraSJ,Activationofthenoradrenergicsystemfacilitatesanattentionalshiftintherat.Behav.BrainRes.,1990Jun1839(1):1928.11. Yu,A.J.Dayan,P.(2005)."Uncertainty,neuromodulation,andattention".Neuron46(4):68192.doi:10.1016/j.neuron.2005.04.026
(https://dx.doi.org/10.1016%2Fj.neuron.2005.04.026).PMID15944135(https://www.ncbi.nlm.nih.gov/pubmed/15944135).12. Johnson,R.Jr(1993)."OntheneuralgeneratorsoftheP300componentoftheeventrelatedpotential".Psychophysiology30(1):9097.
doi:10.1111/j.14698986.1993.tb03208.x(https://dx.doi.org/10.1111%2Fj.14698986.1993.tb03208.x).PMID8416066(https://www.ncbi.nlm.nih.gov/pubmed/8416066).
13. Pineda,J.A.Foote,S.L.Neville,H.J.(1989)."EffectsofLocusCoeruleusLesionsonAuditoryEventRelatedPotentialsinMonkey".J.Neurosci9(1):8193.PMID2563282(https://www.ncbi.nlm.nih.gov/pubmed/2563282).
14. Swick,D.,Pineda,J.a,Schacher,S.,&Foote,S.L.(1994).Locuscoeruleusneuronalactivityinawakemonkeys:relationshiptoauditoryP300likepotentialsandspontaneousEEG.Experimentalbrainresearch.ExperimentelleHirnforschung.Exprimentationcrbrale,101(1),8692.
15. DuncanJohnson,C.C.Donchin,E.(1977)."Onquantifyingsurprise:Thevariationofeventrelatedpotentialswithsubjectiveprobability".Psychophysiology14(5):456467.doi:10.1111/j.14698986.1977.tb01312.x(https://dx.doi.org/10.1111%2Fj.14698986.1977.tb01312.x).PMID905483(https://www.ncbi.nlm.nih.gov/pubmed/905483).
16. Pineda,J.A.,Shafer,K.,&Belamonte,M(1993).NoradrinergicmodulationofauditoryandvisualP300inparietaltemporalcortex.SocietyforNeuroscienceAbstracts,19,1607.
17. Lutzenberger,W.,Elbert,T.,Rockstroth,B.(1987).AbrieftutorialontheimplicationsofvolumeconductionfortheinterpretationoftheEEG.JournalofPsychophysiology,33.S56.
18. Berridge,C.W.,Waterhouse,B.D.(2003)Thelocuscoeruleusnoradrenergicsystem:modulationofbehavioralstateandstatedependentcognitiveprocesses.BrainResearchReviews,42.3384.
19. Usher,M.Cohen,J.D.ServanSchreiber,D.Rajkowski,J.AstonJones,G.(1999)."Theroleoflocuscoeruleusintheregulationofcognitiveperformance".Science283(5401):54954.Bibcode:1999Sci...283..549U(http://adsabs.harvard.edu/abs/1999Sci...283..549U).doi:10.1126/science.283.5401.549(https://dx.doi.org/10.1126%2Fscience.283.5401.549).PMID9915705(https://www.ncbi.nlm.nih.gov/pubmed/9915705).
20. Clayton,E.C.,Rajkowski,J.,Cohen,J.D.,&AstonJones,G.(2004).Phasicactivationofmonkeylocusceruleusneuronsbysimpledecisionsinaforcedchoicetask.J.Neurosci.24(44),991420.
21. Tremblay,L.,Schultz,W.,(1999).Relativerewardpreferenceinprimateorbitofrontalcortex.Nature,398.704708.22. Eisenberger,N.I.Lieberman,M.D.Williams,K.D.(2003)."Doesrejectionhurt?AnFMRIstudyofsocialexclusion".Science302(5643):2902.
Bibcode:2003Sci...302..290E(http://adsabs.harvard.edu/abs/2003Sci...302..290E).doi:10.1126/science.1089134(https://dx.doi.org/10.1126%2Fscience.1089134).PMID14551436(https://www.ncbi.nlm.nih.gov/pubmed/14551436).
23. FalkensteinM,HohnsbeinJ,HoormanJ,BlankeL.(1991).EffectsofcrossmodaldividedattentiononlateERPcomponents:II.Errorprocessinginchoicereactiontasks.Electroencephalogr.Clin.Neurophysiol.78:44755
24. Gehring,WJGoss,BColes,MGHMeyer,DEDonchin,E.(1993)."Aneuralsystemforerrordetectionandcompensation.Psychol".Sci4:38590.25. Barch,DMBraver,TSNystrom,LEForman,SDNoll,DCCohen,JD(1997)."Dissociatingworkingmemoryfromtaskdifficultyinhumanprefrontal
cortex".Neuropsychologia35(10):137380.doi:10.1016/S00283932(97)000729(https://dx.doi.org/10.1016%2FS00283932%2897%29000729).PMID9347483(https://www.ncbi.nlm.nih.gov/pubmed/9347483).
26. Bogacz,R.,Cohen,J.D.,(2004).Parameterizationofconnectionistmodels.Behav.Res.Methods,Instruments,&Computers,36(4),pp.732741.27. Nieuwenhuis,S.AstonJones,G.Cohen,J.D.(2005)."Decisionmaking,theP3,andthelocuscoeruleusnorepinephrinesystem".PsychologicalBulletin
-
3/19/2015 NorepinephrineWikipedia,thefreeencyclopedia
http://en.wikipedia.org/wiki/Norepinephrine 8/8
131(4):51032.doi:10.1037/00332909.131.4.510(https://dx.doi.org/10.1037%2F00332909.131.4.510).PMID16060800(https://www.ncbi.nlm.nih.gov/pubmed/16060800).
28. Brown,E.T.,Gilzenrat,M.S.,&Cohen,J.D.(2004).Thelocuscoeruleus,adaptivegain,andtheoptimizationofsimpledecisiontasks.TechnicalReportNo.0402.
29. Zauner,C.,Schneeweiss,B.,Kranz,A.,Madl,C.,Ratheiser,K.,Kramer,L.,...&Lenz,K.(2000).Restingenergyexpenditureinshorttermstarvationisincreasedasaresultofanincreaseinserumnorepinephrine.TheAmericanjournalofclinicalnutrition,71(6),15111515.
30. Welle,S.,Lilavivat,U.,&Campbell,R.G.(1981).Thermiceffectoffeedinginman:increasedplasmanorepinephrinelevelsfollowingglucosebutnotproteinorfatconsumption.Metabolism,30(10),953958.
31. Rang,H.P.(2003).Pharmacology.Edinburgh:ChurchillLivingstone.ISBN0443071454.Page16732. Unlesselsespecifiedintable,thenrefis:Rang,H.P.(2003).Pharmacology.Edinburgh:ChurchillLivingstone.ISBN0443071454.Page12933. HenekaMT,NadrignyF,RegenT,MartinezHernandezA,DumitrescuOzimekL,TerwelD,JardanhaziKurutzD,WalterJ,KirchhoffF,HanischUK,
KummerMP.(2010).LocusceruleuscontrolsAlzheimer'sdiseasepathologybymodulatingmicroglialfunctionsthroughnorepinephrine.(http://www.pnas.org.libproxy.ucl.ac.uk/content/107/13/6058.full.pdf)ProcNatlAcadSciUSA.17:60586063doi:10.1073/pnas.0909586107(https://dx.doi.org/10.1073%2Fpnas.0909586107)PMID20231476
34. SharmaB,SatishA,KumarR(1999).DictionaryofDrugs(http://books.google.com/?id=3JvArcoG2voC&printsec=frontcover#PPA166).AnmolPublications.ISBN8126118202.
35. GaddumJH(June1956)."ThePrefix'Nor'inChemicalNomenclature".Nature177(1046):10461046.Bibcode:1956Natur.177.1046G(http://adsabs.harvard.edu/abs/1956Natur.177.1046G).doi:10.1038/1771046b0(https://dx.doi.org/10.1038%2F1771046b0).
36. MatthiessenA,FosterGC(1868)."Researchesintothechemicalconstitutionofnarcotineandofitsproductsofdecomposition"(http://books.google.com/?id=tKsOAAAAIAAJ&printsec=titlepage).JournaloftheChemicalSociety358.
37. Thesevaluesarefromratheart.Unlesselsespecifiedintable,thenrefis:Rang,H.P.(2003).Pharmacology.Edinburgh:ChurchillLivingstone.ISBN0443071454.Page167
38. Unlesselsespecifiedintable,thenrefis:Rang,H.P.(2003).Pharmacology.Edinburgh:ChurchillLivingstone.ISBN0443071454.Page16739. Unlesselsespecifiedinboxes,thenrefis:RodFlowerHumphreyP.RangMaureenM.DaleRitter,JamesM.(2007).Rang&Dale'spharmacology.
Edinburgh:ChurchillLivingstone.ISBN0443069115.40. Figure114in:RodFlowerHumphreyP.RangMaureenM.DaleRitter,JamesM.(2007).Rang&Dale'spharmacology.Edinburgh:Churchill
Livingstone.ISBN0443069115.41. "EndokrynologiaKliniczna"ISBN8320008158,page50242. Chapter11in:RodFlowerHumphreyP.RangMaureenM.DaleRitter,JamesM.(2007).Rang&Dale'spharmacology.Edinburgh:Churchill
Livingstone.ISBN0443069115.
Externallinks
MentalHealth:Areportofsurgeongeneral.EtiologyofAnxietyDisorders(http://www.surgeongeneral.gov/library/mentalhealth/chapter4/sec2_1.html)http://www.biopsychiatry.com/nordop.htm
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Categories: Cardiacstimulants Catecholamines Hormonesofthesuprarenalmedulla Neurotransmitters NorepinephrinereleasingagentsTAAR1agonists
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