激动剂作用于胆碱能受体

AgonistsActingon

CholinergicreceptorsCholinomimeticsaretheonesthatmimictheeffectsofACh.Theyareclassifiedbytheirmechanismofaction.ThedrugsaresimilartoAChactions.Cholinoceptor-activatingdrugsCholinoceptorReceptorofAChandothercholinoceptoractivatingagentsMuscarinicreceptorGPCREffectororgan

…heart,exocrinegland,presynapticnerve,endothelialcell(nonerveinnervation)EffectororganwhichisinnervatedbycholinergicsympatheticnerveCNSNicotinicreceptorIonchannellinkedreceptorAutonomicganglia

(bothsym¶sym),Neuromuscularjunction(NMJ)

[skeletalmuscle;somaticnerveinnervation]CNSCholinergicTransmissionAfterreleased,AChbindstoandactivatespre-andpostsynapticAChreceptors,showingtheactionoftransmitter.Then,AChishydrolyzedrapidlybyacetylcholin-esterase(AChE),terminatingtheactionofthetransmitter.WhenanAPreachestheterminal,influxofCa2+istriggered,whichfacilitatesthefusionofthevesicularmembranewiththeterminalmembraneandresultsinthereleaseofAChintosynapticspace.OneAChEcanhydrolyze6x105AChperminute.Somecholinomimeticdrugsbinddirectlytoandactivatecholinoceptors(cholinoceptoragonist)OthersactindirectlybyinhibitingthehydrolysisofendogenousACh(anticholinesterases).Cholinoceptoragonistscanbedividedintotwogroupsbasedonthemodeofaction:cholinoceptoragonistandanticholinesterasesModeofactionofcholinomimeticdrugsDirectactingagentsCholinoceptoractivatingdrugs[Agonist]DirectlybindtocholinoceptorIndirectactingagentsCholinesteraseinhibitingagents[AChEInhibitors]Anti-cholinesteraseInhibitAChhydrolysisIncreaseendogenousAChThemajorgroupsofcholinoceptor-activatingdrugs,receptors,andtargettissues.

BasicPharmacologyof

CholinoceptorAgonists

aredividedintotwogroupsbasedonthechemicalstructureCholineesterAcetylcholine(ACh),MethacholineCarbachol,BethanecholAlkaloidsMuscarine,NicotinePilocarpine,Lobeline,OxotremorineClinicalPharmacologyThemajortherapeuticusesofthecholinoceptor-activatingdrugsarefordiseasesoftheeye,thegastrointestinalandurinarytracts,theneuromuscularjunctionandtheheart.ClinicalUsesaischaracterizedbyincreasedintraocularpressure,whichcanresultinvisionloss.Muscularinicstimulants(pilocarpine)reduceintraocularpressure.A.TheEyeClinicalUses:aTheintraocularpressureisformedbyaqueoushumorwhichisproducedbythebloodvesselsintheciliarybody.Itflowsintoposteriorchamber,throughthepupilintotheanteriorchamber,andthendrainsintotheepiscleralveinviathetrabecularmeshworkandthecanalofSchlemn.Mreceptoragonistscontractionofthesmoothmuscleoftheirissphincter(resultinginmiosis)andoftheciliarymuscle(resultinginmodation)，intraocularpressuredecreasing.B.GastrointestinaltractPilocarpineThedisordersarecharacterizedbydepressionofsmoothmuscleactivity,whichresultindisfunctionofgastrointestinalmovement.Muscularinicstimulantsincreasethetoneandinducemovementofgastrointestine.B.GastrointestinaltractPilocarpine,refluxesophagitis,valveItissometimeusedtoincreasethetoneoftheloweresophagealsphincterinrefluxesophagitis（食管炎）.UrinarytractsMreceptoragonistcanexciteMreceptoronbladdertotreaturinaryretentionwhichmayoccurpost-operativelyorpostpartumorsecondarytospinalcordinjury.Thedrymouth

isduetodecreaseofsalivarysecretion

PilocarpineandcevimelineincreasesalivarysecretionbyexcitingMreceptortotreatdrymouth.

Cholinoceptor-activatingdrugshavebroadeffects.Theselectivityispoor.

Treatmentwiththemdirectedatoneorganalmostalwaysinducesundesirableeffectsinotherorgans.

Thetoxicpotentialvariesdependingontheirabsorption,accesstothecentralnervoussystemandmetabolism.

AdversereactionandtoxicityAcetylcholine(ACh)thenaturallyoccurringneurotransmitterforitsreceptors,hasvirtuallynosystemictherapeuticapplicationsbecauseitsactionsarediffuse,anditshydrolysis,catalyzedbyacetylcholinesterase(AChE),israpid.[Pharmacologicalactions]DirectlyactivateM-R,N-Rmuscarinicactions:smalldosenicotinicactions:largedosePharmacologicalactions

DirectlyactivateM-R,N-Rmuscarinicactions:cardiovascularsystem（CVS）

negativeinotropiceffect（负性肌力）

negativechronotropiceffect（负性心率)negativedromotropiceffect(负性传导)Vasodilation(血管舒张)

a.NOrelease↑b.NArelease↓gastrointestinaltract:motilityincrease,secretionstimulationurinarybladder:detrusormuscle(逼尿肌）contraction,sphincterrelaxationeye:sphinctermuscleofiris(虹膜)

contract:miosisciliarymusclecontract:nearvisionglands↑2.nicotinicactions:largedoseNN-R:dominantnerveactionsNM

-R:skeletalmusclecontraction

alkaloidsPilocarpine（毛果芸香碱，匹鲁卡品）Muscarine（毒蕈碱）

Arecoline（槟榔碱）Oxotremorine（氧化震颤素）(Pilocarpuspennatifolius)

pilocarpinePharmacologicalactions:selectivelyactivateM-R

1.Glandssecreteincreasingly(sweatgland,salivarygland)

2.EyemiosisContractionofthepupillaryconstrictor,areductioninpupilsizemodationCiliarymusclecontractioncausesmodationoffocusfornearvision.decreaseintraocularpressurea（青光眼）

angle-closureaopen-anglea2.iritis（虹膜炎），

iridocyclitis（虹膜睫状体炎）3.others:drymouth

Clinicaluses

Whatisa?increasedpressurewithintheeye.Cellsinsidetheeyeproduceaqueoushumorthatmaintainstheshapeoftheeyeandnourishesthetissuesinsidetheeye.Thebalanceoffluidproductionanddrainageisresponsibleformaintainingnormalpressurewithintheeye.Ina,thedrainescloggedbuttheeyekeepsproducingfluid.Therefore,thepressureintheeyeincreases.Theincreasedpressureintheeyeactuallycancause