03阿托品atropine-山東大學(xué)藥理學(xué)英文課件03IntroductionAChatropine

pharmacologyGeneralintroductionDrugsactingonefferentnervoussystemDrugsactingoncentralnervoussystemDrugsactingoncardiovascularsystemDrugsactingonvisceraChemotherapeuticagentspharmacologyGeneralintroductiChapter5IntrductiontoPharmacology

ofEfferentNervousSystemZhangBinInstituteofPharmacologySchoolofMedicineShandongUniversityChapter5IntrductiontoPharOrganizationofNervoussystemOrganizationofNervoussystemefferentnervoussystem(ENS)

autonomicnervoussystem(vegetativenervoussystem)somaticmotornervoussystem

efferentnervoussystem(ENS)

Efferentneuronsoftheautonomic

nervoussystemEfferentneuronsoftheautonoClassificationofENSaccordingtothereleasedneurotransmitters

cholinergicnerve:acetylcholine(Ach)

noradrenergicnerve:noradrenaline(NA)

ClassificationofENSaccordin03阿托品atropine——山東大學(xué)藥理學(xué)英文課件03IntroductionAChatropineClassificationofENSParasympatheticnerveCentralnervoussystem

Achskeletalmuscle

AchNA

AchAchsweatglands

Ach

AchAchadrenalmedullasomaticmotornerve

sympatheticnerveglands,smoothmuscle,heartheart,vessel,smoothmuscleClassificationofENSParasympSection1Neurotransmitterand

ReceptorofENS

NeurotransmitterofENSThereceptorsofENSSection1Neurotransmitte一.NeurotransmitterofENS1.Developmentofneurotransmittertheory100yearsagoChemicaltransmissionelectronictransmission1946VonEulerNA(noradrenaline)1921loewidoublefrogheartexperiment1926DaleAch(acetylcholine)一.NeurotransmitterofENS1.De03阿托品atropine——山東大學(xué)藥理學(xué)英文課件03IntroductionAChatropine2.Biosynthesis,storage,releaseandterminationofneurotransmittersAch(acetylcholine)NA(noradrenaline)2.Biosynthesis,storage,releainhibitorinhibitor03阿托品atropine——山東大學(xué)藥理學(xué)英文課件03IntroductionAChatropine2.Biosynthesis,storage,releaseandterminationofneurotransmitters

(1)Biosynthesischoline+acetylcoenzymeAAchtyrosinedopaDANAcholineacetylaseTHDDDH2.Biosynthesis,storage,relea(2)Storage

+ATP+proteinstoreinvesicles

AchNA(2)StorageAchNA(3)releaseexocytosisquantalrealeasecotransmission(3)releaseexocytosis(4)Termination

Ach:

acetylcholinesterase(AchE)insynapseNA:

uptake1(neuronaluptake)75%-90%storageinvesicles\MAOuptake2(non-neuronaluptake)COMT\MAO

(4)Termination

Ach:acetylchol二.ThereceptorsofENS

Classification,DistributionandEffect二.ThereceptorsofENSClassiCholinereceptors(Cholinoceptors)M-R:

muscarineN-R:nicotine

Cholinereceptors(Cholinocep03阿托品atropine——山東大學(xué)藥理學(xué)英文課件03IntroductionAChatropineCholinoceptorsM-R:M1-R:ganglion,CNSM2-R:heart,presynapticsites(negativefeedback),CNSM3-R:exocrineglands,smoothmuscle,endothelium,CNSM4–R:exocrineglands,smoothmuscle,CNSM5-R:CNSCholinoceptorsM-R:CholinoceptorsN-R:nicotineNM-R:skeletalmuscle

NN-R:ganglionandCNSCholinoceptorsN-R:nicotinadrenoceptor:NAAD

α-Rα1-R:

postsynapticeffectorcells

(especiallysmoothmuscle)α2-R:

presynapticnerveterminals(negativefeedback),platelet,smoothmuscle,lipocytesadrenoceptor:NAADα-Radrenoceptorβ-Rβ1-R:postsynapticeffectorcells,(especiallyheart,lipocytes,)

presynapticnerveterminalsβ2-R:postsynapticeffectorcells,(especiallysmoothmuscle)β3-R:postsynapticeffectorcells,

(especiallylipocytes)adrenoceptorβ-R03阿托品atropine——山東大學(xué)藥理學(xué)英文課件03IntroductionAChatropineClassificationofreceptoraccordingtotheirstructureG-protein-coupledreceptor:

-R,-R,M-R,DA-R,5-HT-RLigand-gatedreceptors

N-RClassificationofreceptoraccStructureofG-protein-coupledReceptorStructureofG-protein-coupledMolecularMechanismofGq-protein-coupledReceptorMolecularMechanismofGq-protMolecularMechanismofGi/s-protein-coupledReceptorMolecularMechanismofGi/s-prStructureofligand-gatedionchannelReceptorStructureofligand-gatedionMolecularMechanismofligand-gatedionchannelreceptorMolecularMechanismofligand-1.Cholinoceptors

M-R:G-protein-coupledreceptor

M1-R:Gq-protein-coupledreceptor

M2-R-Gi-protein-coupledreceptor

N-R:ligand-gatedionchannelreceptor2.

adrenoceptor:

G-protein-coupledreceptorα1–R:Gq-protein-coupledreceptorα2–R:Gi-protein-coupledreceptorβ-R:Gs-protein-coupled

receptor1.CholinoceptorsMolecularMechanismofReceptor

N-RNa+,K+,

Ca2+G-protein-coupledreceptor

ligand-gatedreceptor:(-)

PKA

cAMPM1-R

M2-R

GqGiK+,

Ca2+(-)AC

cAMPPLC

IP3DAGα1

-R

α2

-R

β-R(+)

AC

(-)

AC

GiGqPLC,PLA2,PLD

GscAMP(-)

PKA

(+)

PKA

Ca2+(+)

PKCMolecularMechanismofReceptoterminologyadrenergicadrenergicreceptorcholinergiccholinergicreceptorpostsynapticreceptorpresynapticreceptorterminologyadrenergicSection2

Thephysiological

actionsofENSCo-innervationandDominantTheorySympatheticactions:

fightandflightresponseParasympatheticactions:

restanddigestresponseSection2

ThephysiologicalacSection3Thebasicmechanismsof

actionsofENSdrugs

1.Directactionofreceptors

agonistblocker(antagonist)2.lnfluenceofneurotransmitters

biosynthesisreleasestorageconversionSection3Thebasicmechanisms

Section4Theclassificationofthe

ENSdrugs

Section4Theclassification（三）抗膽堿酯酶藥（三）抗膽堿酯酶藥Chapter6parasympathomimeticsCholinoceptoragonists(cholinomimetics)Anticholinesteraseagents(cholinesterase-inhibitingdrugs)DrugsofenhancersofAChreleaseChapter6parasympathomimeticsCholinoceptorAgonists

M-Ragonists:

Cholineesters:acetylcholine(ACh)

alkaloids:pilocarpineN-Ragonists:

nicotine

CholinoceptorAgonists

M-RagoSection1M-Ragonists

Acetylcholine(ACh)1.unstable2.lowselectivity3.administrationrouteSection1M-RagonistsAcety[Pharmacologicalactions]DirectlyactivateM-R,N-Rmuscarinicactions:smalldosenicotinicactions:largedose[Pharmacologicalactions]1.muscarinicactions:smalldose

1.cardiovascularsystemvesseldilate

a.NOrelease↑(M3R→EDRF(NO)↑→GC→cGMP↑→intracellularCa2+↓)b.NArelease↓

BP(HR)

Heartdepress:negative(chronotropic,dromotropic,inotropic)effect1.muscarinicactions:smalldo1.muscarinicactions:smalldose2.glands↑3.gastrointestinaltract:

motilityincrease,secretionstimulation4.urinarybladder:

detrusormuscle(逼尿?。ヽontraction,trigoneandsphincterrelaxation5.eye:

sphinctermuscleofiris(虹膜）contract:miosisciliarymusclecontract:nearvision1.muscarinicactions:smalldo2.nicotinicactions:largedoseNN-R:dominantnerveactionsNM

-R:skeletalmusclecontraction

2.nicotinicactions:largedose03阿托品atropine——山東大學(xué)藥理學(xué)英文課件03IntroductionAChatropine03阿托品atropine——山東大學(xué)藥理學(xué)英文課件03IntroductionAChatropinealkaloidsPilocarpine（毛果蕓香堿，匹魯卡品）Muscarine（毒蕈堿）

Arecoline

（檳榔堿）Oxotremorine（氧化震顫素）alkaloidsPilocarpine（毛果蕓香堿，匹魯卡Pilocarpine

Pharmacologicalactions:selectivelyactivateM-R

1.Eye

miosis:pupiliarysphincter

decreaseintraocularpressurespasmofaccommadation:ciliarymuscle

Pilocarpine

Pharmacologicalac03阿托品atropine——山東大學(xué)藥理學(xué)英文課件03IntroductionAChatropine03阿托品atropine——山東大學(xué)藥理學(xué)英文課件03IntroductionAChatropine2.Glandssecreteincreasingly

(sweatgland,salivarygland)3.Smoothmuscle4.Cardiovascularsystem2.GlandssecreteincreasinglClinicaluses

1.Glaucoma(青光眼）angle-closureglaucomaopen-angleglaucomaClinicaluses1.Glaucoma(青光眼）WhatisGlaucoma?increasedpressurewithintheeye.Cellsinsidetheeyeproduceaqueoushumorthatmaintainstheshapeoftheeyeandnourishesthetissuesinsidetheeye.Thebalanceoffluidproductionanddrainageisresponsibleformaintainingnormalpressurewithintheeye.Inglaucoma,thedrainbecomescloggedbuttheeyekeepsproducingfluid.Therefore,thepressureintheeyeincreases.TheincreasedpressureintheeyeactuallycancausetheeyetostretchandenlargeWhatisGlaucoma?increasedpreHowdoesGlaucomaaffecttheeye?VisionLoss.Pressuredamagetotheopticnerveanddecreasedbloodflowtotheretina,resultsinlossofvision.However,ifthepressureintheeyeremainsuncontrolled,theretinadegeneratesandvisionispermanentlylost.PermanentblindnesscanoccurwithinseveralhoursifthepressureisveryhighandtheglaucomadevelopsrapidlyPain.Humanshavenormalintraocularpressuresbetween10and20mmHg.Glaucomaoftenresultsinpressuresof20-28mmHginhumans.Thepainpersistsintheformofaconstantheadacheormigraine.Thisdiscomfortcanresultindecreasedactivity,lessdesiretoplay,irritability,ordecreasedappetiteHowdoesGlaucomaaffectthee2.iritis（虹膜炎），iridocyclitis（虹膜睫狀體炎）3.others

:drymouth2.iritis（虹膜炎），Adversereactions

AdversereactionsMuscarine（毒蕈堿）Amanitamuscaria（捕蠅蕈）Inocybe（絲蓋傘菌屬）Clitocybe（杯傘菌屬）Muscarine（毒蕈堿）AmanitamuscariaSection2N-Ragonists

——nicotineNicotine:fromtobaccoAction:NM,NN,CNSanddependence(doublephase)Tobaccopoison:

Hypertension,coronaryheartdisease,cerebrovasculardisease,cancer,AtherosclerosisSection2N-Ragonists

——niChina:Largesttobaccoproductivecountry,LargesttobaccoconsumptioncountryNosmoking！Stopsmoking！China:LargesttobaccoproductiSection3

AnticholinesteraseAgentsCholinesterase:trueCholinesterase(AChE)PseudocholinesteraseSection3

Anticholinesterase03阿托品atropine——山東大學(xué)藥理學(xué)英文課件03IntroductionAChatropineAnticholinesteraseAgents

-----indirectactingcholinomimetics

AnticholinesteraseAgents

----Classificationaccordingtostructurenon-covalentbondingagents:

Edrophoniumchloride(依酚氯銨):strongpolarity,short

tacrine(他克林):stronglipophilia,long

donepezil(多奈哌齊):stronglipophilia,longCarboxamide(氨甲酰類):

Physostigmine(毒扁豆堿)

Pyridostigmine(吡斯的明)Demecarium(地美溴銨)rivastigmine(利凡斯的明)orgnaophosphoruscompound(有機磷化合物)Classificationaccordingtost親和力親脂性BBB維持時間依酚氯銨一般弱—短他克林較高強＋長多奈哌齊較高強＋長親和力親脂性BBB維持時間依酚氯銨一般弱—短他克林較高強＋長ClassificationaccordingtopharmacologicalpropertyReversibleAnticholinesteraseagentsirreversibleAnticholinesteraseagents

ClassificationaccordingtophMechanismsofactions:Pharmacologicalactions:

1.eye2.gastrointestinaltract（esophagus,stomach,intestine)3.motorendplate4.glands5.cardiovascularsystemMechanismsofactions:ClinicalUses

1.Myastheniagravis(重癥肌無力):NeostigminePyridostigmine(吡斯的明)Ambenoniumchloride(安貝氯胺)

ClinicalUses1.Myastheniagr03阿托品atropine——山東大學(xué)藥理學(xué)英文課件03IntroductionAChatropineClinicalUses2.Postoperativeabdominaldistension;Urinaryretention:Neostigmine3.glaucoma:Physostigmine(毒扁豆堿)Demecarium(地美溴銨)

ClinicalUses2.Poxicationofd-tubocurarine:Neostigmine，Edrophoniumchloride(依酚氯銨):5.Alzheimer’sdisease:

tacrine,donepezil,

rivastigmine,galanthamin

6.Soxicationofd-tubocurar

CommonusedagentsReversibleAnticholinesteraseagents

CommonusedagentsReversibl

Neostigmine(新斯的明）actions：1.InhibitAChE2.ActivateNM-Ronmotorendplate3.Strongeffectonskeletalmuscle4.NotintoCNS

Neostigmine(新斯的明）actions：Uses:1.Myastheniagravis:Skeletalmusclecontraction

po,sc,imiv2.Postoperativeabdominaldistension;Uoxicationofd-tubocurarineandatropine4.Supraventriculartachyarrhythmias5.GlaucomaUses:Adversereactions:

Cholinergicoverexcitation(cholinergiccrisis)Treatment:atropine

d-tubocurarine

Adversereactions:Pyridostigmine(吡斯的明)WeakerthanNeostigmineslowerthanNeostigmineLongerthanNeostigmineNotintoCNSUsedtotreatMyastheniagravisContraindication:mechanicalileus，urinaryobstructionPyridostigmine(吡斯的明)WeakerthPhysostigminecharacteristics1.Strongerthanneostigmine2.CanenterCNS3.HavenodirectactiononRPhysostigminecharacteristicsactions：1.eye2.systemicactionUses:1.Glaucoma2.Intoxicationofanticholineagents:

Atropine

TricyclicantidepressantDibenzothiazineantipsychotics

actions：Comparisontopilocarpine1.Morerapid2.Stronger3.longerComparisontopilocarpineDonepezilRivastigmineTacrine

——Alzheimer’sdiseaseDonepezilReversibleanticholinesteraseagentsneostigmine\Pyridostigmine\Ambenonium\Galanthamine:MyastheniagravisPhysostigmine\Demecarium:Glaucoma

Edrophoniumchloride:diagnostictestformyastheniagravisDonepezil\rivastigmine\Tacrine\:Alzheimer’sdiseaseReversibleanticholinesteraseIrreversibleAnticholinesteraseAgents--Organophosphates

MechanismsofintoxicationPathwayofintoxication

signsofacuteintoxication1.Mmanifestation(muscarinicexcess)2.Nmanifestation(nicotiniceffects)3.CNSeffectsChronicintoxication

IrreversibleAnticholinesteras03阿托品atropine——山東大學(xué)藥理學(xué)英文課件03IntroductionAChatropinePreventionandtreatmentof

organophosphatesintoxication

PreventionTreatmentofacuteintoxication

1.maintenanceofvitalsigns2.Decontaminationtopreventfurtherabsorption3.Symptomatictreatment1)atropine2)cholinesterasereactivator

Preventionandtreatmentof

oCholinesteraseReactivators

Pralidoximeiodide(PAM):碘解磷定Mechanismsofactiontherapeuticeffect

1.inhibitNmmanifestation——strong2.inhibitMmanifestation——weak3.CNS

碘解磷定磷酰化AChE復(fù)合物磷?；饨饬锥ˋChECholinesteraseReactivators

PrPralidoximechloride

(PAM-Cl):氯解磷定betterwater-solubilityimandivlittleadversereactionPralidoximechloride(PAM-Cl):03阿托品atropine——山東大學(xué)藥理學(xué)英文課件03IntroductionAChatropineChapter7cholinoceptor-blockingdrugsM-RblockersN-Rblockers:NN-RblockersNM-RblockersChapter7cholinoceptor-blockiMuscariniccholinoceptor

-blockingdrugs

Atropineandatropine-likealkaloidsSyntheticatropinesubstitutesMuscariniccholinoceptor

-bloatropine-likealkaloidsandtheirresources植物主要生物堿

顛茄(atropabelladonna)莨菪堿(hyoscyamine)曼陀羅(daturastramonium)莨菪堿洋金花(datruasp)東莨菪堿

(scopolamine)莨菪(hyoscyamusniger)莨菪堿

唐古特莨菪(scopoliatangutica)山莨菪堿

(anisodamine)

樟柳堿(anisodineatropine-likealkaloidsand顛茄莨菪顛茄莨菪曼陀羅洋金花曼陀羅洋金花Atropine

pharmacologicalactions:

blockM-RblockNN-RinlargedoseAtropine

pharmacologicalactio03阿托品atropine——山東大學(xué)藥理學(xué)英文課件03IntroductionAChatropinepharmacologicalactions1.glands:

secretion↓salivary,sweat>lacrimal,respiratory>gastricacid,pancreatic,intestinaljuice2.eyes

(1)mydriasis(2)increaseintraocularpressure(3)paralysisofaccommodationpharmacologicalactions1.glan03阿托品atropine——山東大學(xué)藥理學(xué)英文課件03IntroductionAChatropine3.splanchnic

smoothmuscle:relaxation

(spasmodic)GItract,detrusormuscleofbladder:significant

Biletract,bronchial,uterine(子宮):weak3.splanchnicsmoothmuscle:r4.heart:(1)HR

Therapeuticdose:decrease

(presynapticM1blockade)Largedose:increase(blockvagaleffectonM2–R)(2)A-Vconduction:4.heart:5.vessels:dilation(inlargedose)

(1)Directeffect(2)Compensativereactionbytemperaturerise6.CNS:excitation5.vessels:dilation(inlarge03阿托品atropine——山東大學(xué)藥理學(xué)英文課件03IntroductionAChatropineOrgansensitivity:Gland＞eye＞splanchnicsmoothmuscle＞cardiovascularsystem＞CNS.Organsensitivity:ClinicalUses1.Anti-smoothmusclespasm2.

Pre-anaesthesiamedicationagent3.

Ophthalmologicaluse(1)iridocyclitis

(2)optometry

(3)examinationofretina4.Bradyarrhythmias5.

Shock(septicshock):Cautions6.IntoxicationoforganophosphateClinicalUses1.Anti-smoothmuadversereactions1.CommonSideEffectsadversereactions1.CommonSid2.AcutePoisoningminimallethaldose:adults–80~130mgchildren--10mgPrevention1.Decontamination:topreventfurtherabsorption2.Antidotes:

Parasympathomimetics3.Maintenanceofvitalsigns2.AcutePoisoningcontraindictions

Glaucomaprostatichypertrophy

contraindictionsanisodamine(654-2)

山莨菪堿Characteristicofactions1.highselectivity(smoothmuscleandvessels)2.littlesideeffect(notpassthroughBBB)Uses1.septicshock2.visceralcolics.anisodamine(654-2)

山莨菪堿Charact

Scopolamine(東莨菪堿)

[Characteristics]1.CNSactions:depression(strong)

2.peripheralactions:glands:strongothers:weakUses:1.preanaesthesiamedication2.preventionmotionsickness

3.Parkinsondisease

4.traditionalmedicineanaesthesia

Scopolamine(東莨菪堿)

[Character中藥麻醉華佗（公元141～203年）“麻沸散”

曼陀羅(洋金花)徐州醫(yī)學(xué)院附屬醫(yī)院:中藥麻醉湯(針劑)東莨菪堿中藥麻醉華佗（公元141～203年）Section2SyntheticatropinesubstitutesSyntheticMydriaticsSyntheticAntispasmaticsSelectiveM1AntagonistsSection2SyntheticatropinesSyntheticMydriaticsHomatropine(后馬托品)Tropicamide(托吡卡胺)Cyclopentolate(環(huán)噴托酯)Eucatropine(尤卡托品)SyntheticMydriaticsHomatropinComparisonofsomemydriaticsdrugsconcentration(%)mydriasisparalysisofaccommodationpeak(m)duration(d)peak(h)duration(d)atropine1.030~407~101~37~12homatropine1.0~2.040~601~20.5~11~3tropicamide0.5~1.020~400.250.5<0.25cyclopentolate0.530~50110.25~1eucatropine2.0~5.0301/12~1/4ComparisonofsomemydriaticscUses:iridocyclitis

optometry

examinationofretinaUses:SyntheticAntispasmaticsQuaternaryamines(季胺類)：

Propanthelinebromide(溴丙胺太林，普魯本辛)1.selectiveblockadeofGItract:2.ulceration,GIspasm,bladderstimulation3.neuromuscularblockaction:toxicdose4.lowBBBpermeability

SyntheticAntispasmaticsQuaterQuaternaryamines(季胺類)：Ipratropiumbromide(異丙托溴胺)1.Relievebronchospasmbyinhalation2.Uses:chronicobstructivepulmonarydisease,bronchialasthma3.ganglionicblockactionstrongerthanatropine4.lowBBBpermeabilityQuaternaryamines(季胺類)：Tertiaryamines(叔胺類)：MydriaticsAnticholinergicinCNS

Antispasmaticagents

Benactyzine(貝那替嗪，胃復(fù)康）1.Relievesmoothmusclespasm2.AntianxietyeffectTertiaryamines(叔胺類)：SelectiveM1AntagonistsPirenzepine(哌侖西平)Telenzepine(替侖西平)InhibitsecretionofgastricacidClinicaluse:pepticulcerNotintoCNSSelectiveM1AntagonistsPirenz03阿托品atropine——山東大學(xué)藥理學(xué)英文課件03IntroductionAChatropine受體亞型分布效應(yīng)N1受體N2受體M1受體M2受體M3受體神經(jīng)節(jié)腎上腺髓質(zhì)骨骼肌神經(jīng)節(jié)竇房節(jié)房室節(jié)心肌平滑肌外分泌腺神經(jīng)節(jié)除極兒茶酚胺釋放骨骼肌收縮介導(dǎo)遲發(fā)性興奮突觸后電位延緩自發(fā)除極，減慢心率減慢傳導(dǎo)速度降低收縮力收縮分泌增多受體亞型分布效應(yīng)N1受體神經(jīng)節(jié)神經(jīng)節(jié)除極受體亞型分布效應(yīng)1受體2受體1受體2受體3受體血管平滑肌生殖道泌尿道平滑肌肝臟小腸平滑肌心臟胰島細(xì)胞血管平滑肌血小板神經(jīng)末梢心臟腎小球旁器細(xì)胞平滑肌肝臟脂肪組織收縮收縮肝糖原分解松弛增強收縮力減少胰島素分泌收縮聚集減少去甲腎上腺素釋放興奮增加腎素分泌松弛肝糖原分解脂肪分解受體亞型分布效應(yīng)1受體血管平滑肌收縮03阿托品atropine——山東大學(xué)藥理學(xué)英文課件03IntroductionAChatropine03阿托品atropine——山東大學(xué)藥理學(xué)英文課件03IntroductionAChatropine03阿托品atropine——山東大學(xué)藥理學(xué)英文課件03IntroductionAChatropine03阿托品atropine——山東大學(xué)藥理學(xué)英文課件03IntroductionAChatropinepharmacologyGeneralintroductionDrugsactingonefferentnervoussystemDrugsactingoncentralnervoussystemDrugsactingoncardiovascularsystemDrugsactingonvisceraChemotherapeuticagentspharmacologyGeneralintroductiChapter5IntrductiontoPharmacology

ofEfferentNervousSystemZhangBinInstituteofPharmacologySchoolofMedicineShandongUniversityChapter5IntrductiontoPharOrganizationofNervoussystemOrganizationofNervoussystemefferentnervoussystem(ENS)

autonomicnervoussystem(vegetativenervoussystem)somaticmotornervoussystem

efferentnervoussystem(ENS)

Efferentneuronsoftheautonomic

nervoussystemEfferentneuronsoftheautonoClassificationofENSaccordingtothereleasedneurotransmitters

cholinergicnerve:acetylcholine(Ach)

noradrenergicnerve:noradrenaline(NA)

ClassificationofENSaccordin03阿托品atropine——山東大學(xué)藥理學(xué)英文課件03IntroductionAChatropineClassificationofENSParasympatheticnerveCentralnervoussystem

Achskeletalmuscle

AchNA

AchAchsweatglands

Ach

AchAchadrenalmedullasomaticmotornerve

sympatheticnerveglands,smoothmuscle,heartheart,vessel,smoothmuscleClassificationofENSParasympSection1Neurotransmitterand

ReceptorofENS

NeurotransmitterofENSThereceptorsofENSSection1Neurotransmitte一.NeurotransmitterofENS1.Developmentofneurotransmittertheory100yearsagoChemicaltransmissionelectronictransmission1946VonEulerNA(noradrenaline)1921loewidoublefrogheartexperiment1926DaleAch(acetylcholine)一.NeurotransmitterofENS1.De03阿托品atropine——山東大學(xué)藥理學(xué)英文課件03IntroductionAChatropine2.Biosynthesis,storage,releaseandterminationofneurotransmittersAch(acetylcholine)NA(noradrenaline)2.Biosynthesis,storage,releainhibitorinhibitor03阿托品atropine——山東大學(xué)藥理學(xué)英文課件03IntroductionAChatropine2.Biosynthesis,storage,releaseandterminationofneurotransmitters

(1)Biosynthesischoline+acetylcoenzymeAAchtyrosinedopaDANAcholineacetylaseTHDDDH2.Biosynthesis,storage,relea(2)Storage

+ATP+proteinstoreinvesicles

AchNA(2)StorageAchNA(3)releaseexocytosisquantalrealeasecotransmission(3)releaseexocytosis(4)Termination

Ach:

acetylcholinesterase(AchE)insynapseNA:

uptake1(neuronaluptake)75%-90%storageinvesicles\MAOuptake2(non-neuronaluptake)COMT\MAO

(4)Termination

Ach:acetylchol二.ThereceptorsofENS

Classification,DistributionandEffect二.ThereceptorsofENSClassiCholinereceptors(Cholinoceptors)M-R:

muscarineN-R:nicotine

Cholinereceptors(Cholinocep03阿托品atropine——山東大學(xué)藥理學(xué)英文課件03IntroductionAChatropineCholinoceptorsM-R:M1-R:ganglion,CNSM2-R:heart,presynapticsites(negativefeedback),CNSM3-R:exocrineglands,smoothmuscle,endothelium,CNSM4–R:exocrineglands,smoothmuscle,CNSM5-R:CNSCholinoceptorsM-R:CholinoceptorsN-R:nicotineNM-R:skeletalmuscle

NN-R:ganglionandCNSCholinoceptorsN-R:nicotinadrenoceptor:NAAD

α-Rα1-R:

postsynapticeffectorcells

(especiallysmoothmuscle)α2-R:

presynapticnerveterminals(negativefeedback),platelet,smoothmuscle,lipocytesadrenoceptor:NAADα-Radrenoceptorβ-Rβ1-R:postsynapticeffectorcells,(especiallyheart,lipocytes,)

presynapticnerveterminalsβ2-R:postsynapticeffectorcells,(especiallysmoothmuscle)β3-R:postsynapticeffectorcells,

(especiallylipocytes)adrenoceptorβ-R03阿托品atropine——山東大學(xué)藥理學(xué)英文課件03IntroductionAChatropineClassificationofreceptoraccordingtotheirstructureG-protein-coupledreceptor:

-R,-R,M-R,DA-R,5-HT-RLigand-gatedreceptors

N-RClassificationofreceptoraccStructureofG-protein-coupledReceptorStructureofG-protein-coupledMolecularMechanismofGq-protein-coupledReceptorMolecularMechanismofGq-protMolecularMechanismofGi/s-protein-coupledReceptorMolecularMechanismofGi/s-prStructureofligand-gatedionchannelReceptorStructureofligand-gatedionMolecularMechanismofligand-gatedionchannelreceptorMolecularMechanismofligand-1.Cholinoceptors

M-R:G-protein-coupledreceptor

M1-R:Gq-protein-coupledreceptor

M2-R-Gi-protein-coupledreceptor

N-R:ligand-gatedionchannelreceptor2.

adrenoceptor:

G-protein-coupledreceptorα1–R:Gq-protein-coupledreceptorα2–R:Gi-protein-coupledreceptorβ-R:Gs-protein-coupled

receptor1.CholinoceptorsMolecularMechanismofReceptor

N-RNa+,K+,

Ca2+G-protein-coupledreceptor

ligand-gatedreceptor:(-)

PKA

cAMPM1-R

M2-R

GqGiK+,

Ca2+(-)AC

cAMPPLC

IP3DAGα1

-R

α2

-R

β-R(+)

AC

(-)

AC

GiGqPLC,PLA2,PLD

GscAMP(-)

PKA

(+)

PKA

Ca2+(+)

PKCMolecularMechanismofReceptoterminologyadrenergicadrenergicreceptorcholinergiccholinergicreceptorpostsynapticreceptorpresynapticreceptorterminologyadrenergicSection2

Thephysiological

actionsofENSCo-innervationandDominantTheorySympatheticactions:

fightandflightresponseParasympatheticactions:

restanddigestresponseSection2

ThephysiologicalacSection3Thebasicmechanismsof

actionsofENSdrugs

1.Directactionofreceptors

agonistblocker(antagonist)2.lnfluenceofneurotransmitters

biosynthesisreleasestorageconversionSection3Thebasicmechanisms

Section4Theclassificationofthe

ENSdrugs

Section4Theclassification（三）抗膽堿酯酶藥（三）抗膽堿酯酶藥Chapter6parasympathomimeticsCholinoceptoragonists(cholinomimetics)Anticholinesteraseagents(cholinesterase-inhibitingdrugs)DrugsofenhancersofAChreleaseChapter6parasympathomime