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药物的抗惊厥作用VIP免费

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AnticonvulsantEffectsofDrugsXXX(ChinaPharmaceuticalUniversity,639LongmianAvenue,Nanjing,Jiangsu,China210009)ABSTRACT:OBJECTIVE:TostudytheanticonvulsantefficacyofPhenytoinsodiumandPhenobarbitalandvalproateonconvulsion.METHODS:Theanticonvulsantactivityofthedrugswasevaluatedbythemaximalelectroshock(MES)testandremeflinseizuretest.Inducedratsweretreatedbyintraperitonealinjection,thenobservetheincubationperiod(uptotailsupright45°)anddegreeofreactionofeachmouse(spasm,fallingdown,stiffordeath).RESULTS:1.InMESexperiment,thedegreeofconvulsion:ThePhenobarbitalgroup(P<0.05vsnormalsalinegroup)wasthelightest,andtheNSgroupwastheseverestone.2.Inremeflinexperiment,thesimilarresultwasobservedbetweenvalproategroupandNSgroup(P<0.01).CONCLUSION:Phenobarbitalhasbetteranti-convulsioneffectthanPhenytoinsodiumonconvulsioninducedbyelectroshock,andvalproatehasasignificanteffecttoanti-convulsioninducedbyremeflin.KEYWORDSPhenytoinsodium;Phenobarbital;valproate;remeflin;anti-convulsionIntroductionPhenytoinsodium:itsmechanismofaction:Itcanblocksodiumchannels(voltage-,frequency-,andtimedependentfashion)andinhibitthegenerationofactionpotentialsandItcanincreasethefunctionofinhibitorytransmitterGABA,inhibitnerveterminaltouptakeGABAandinducetheincreasingofGABAreceptor,therebyenhanceGABA-mediatedpostsynapticinhibition.Phenobarbital:itsmechanismofaction:Phenobarbitalcaninhibittheparadoxicaldischargeofepilepsyfocusselectively,enhancestimulationofsurroundingtissuesandblockdischargediffusetonormaltissuesandPhenobarbitalfacilitateGABA-mediatedinhibitionofneuronalactivity.Valproateisbroadspectrumantiepilepticdrug,whichisusedtoalltypesofepilepsy;itsmechanismisthatenhancingtheenzymaticactivityofglutamatedecarboxylase.AndInhibitingGABAreuptakeandsynapseinactivationviareleasingsynapsefrontalmembraneGABAandthenenhanceGABApostsynapticinhibitionRemeflin,acentralstimulatewhichcandirectlyexciterespiratorycenter,canproduceconvulsionwithover-dose.Theprotectiveeffectsofdrugsonconvulsionproducedbyremeflincanbeusedtoscreenantiepilepticandanti-convulsion.Stimulatingmouseheadwithastrongelectriccurrentcancausegeneraltetanicconvulsion.Ifadrugcanpreventtheoccurrenceofgeneraltitanicconvulsion,wecouldinitiallysuspectthatithasantagonisticeffectongrandmal.Remeflin,acentralstimulantwhichcandirectlyexciterespiratorycenter,canprotectiveeffectsofdrugsonconvulsionproducedbyremeflincanbeusedtoscreenantiepilepticsandanticonvulsants.[1]1MaterialEquipmentsBalance,syringes,pharmacologicalandphysiologicalmultipurposeapparatusReagentsPhenytoinsodium,0.5%solutionw/v,Phenobarbitalsodium,0.5%solutionw/v,0.04%Remeflin,2%sodiumvalporate,normalsalineAnimals5mice,18-22g,norestrictiononsex2Methods2.2MethodsofMESexperimentAdjustthestimulatorfirstly.Stimulatingparameters:workingcondition---electricshock;outputvoltage--maximum;modelofstimulating--single;frequency--32~16Hz;connecttheoutletwithclipsandplugtheconnectionforpower.Selectconvulsionmice.Attachtheclipsmoistenedwithsalinetothemouseears.Punchthekeytostarting,andacurrentisappliedtotheheadofthemouse,thencausetonicconvulsionthatisthestateoftheflexingforelimbandstraighteninghindlimb.Iftheanimalsdon’tfallintoconvulsionwith32Hz,modulateto16Hz,andstartagain.Replaceanotheronetotestifhavenoreaction,yet.Selectthreemiceinwhichconvulsionsoccurtypically.Markandweighthem.Treatthembyintraperitonealinjectionof5%...

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药物的抗惊厥作用

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