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**Slide5Thisslidedepictsourcurrentunderstandingoftheneurotransmittersinvolvedinchemotherapy-inducednauseaandvomiting(CINV),includingthemostrecentlyidentifiedemeticneurotransmitter,substanceP.1–3Peripheralneuroreceptorsandthechemoreceptortriggerzone(CTZ)areknowntocontainreceptorsforserotonin,substanceP,dopamine,histamine,andotherendogenousneurotransmitters.Whenthesereceptorsareactivated,emesisisinduced.1,2Inthepast15yearsorso,enormousadvanceshavebeenmadeinourunderstandingoftheneurochemicalpathwaysinvolvedinCINV.Theadventofselective5-HT3receptorantagonistshasservedasapharmacologictoolforstudyingtheemeticpathwaysassociatedwithCINV.TheintroductionofthisclassofdrugsstimulatedconsiderableclinicalresearchandimprovedourunderstandingofCINV.4Wheretheoriginalpreclinicalefficacytrialsof5-HT3receptorantagonistsonceinvolvedanobservationperiodof4hours,4todaywehaveabetterappreciationofdelayedsymptoms,whichcanspanseveraldaysfollowingchemotherapy.ThediscoveryofsubstancePwasfirstreportedin1931.Some70yearslater,wenowunderstandthatthisneurotransmitterplaysanintegralroleinrelayingnoxioussensoryinformationtothebrain.Asamodulatorofnociception,itisinvolvedinseveralphysiologicactivities,includingthevomitingreflex.5ReferencesDiemunschP,GrélotL.PotentialofsubstancePantagonistsasantiemetics.Drugs2000;60:533–546.GrunbergSM,HeskethPJ.Controlofchemotherapy-inducedemesis.NEnglJMed1993;329:1790–1796.HornbyPJ.Receptorsandtransmissioninthebrain-gutaxis.II.Excitatoryaminoacidreceptorsinthebrain-gutaxis.AmJPhysiolGastrointestLiverPhysiol
2001;280:G1055–G1060.AndrewsPL,NaylorRJ,JossRA.Neuropharmacologyofemesisanditsrelevancetoanti-emetictherapy.SupportCareCancer1998;6:197–203.DeVaneCL.SubstanceP:Anewera,anewrole.Pharmacoth
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