胆碱受体激动药Chapter-7

胆碱受体激动药Chapter-7第一页，共18页。第一节

M胆碱受体激动药AcetylcholinereceptoragonistsarechemicalsthatrecognizeanddirectlybindtotheAChRsinthecentralandperipheralnervoussystems.ThesedrugsmimictheeffectsofAChandsocausemuscariniceffectsornicotiniceffectsintheperipheralandcentralnervoussystems.第二页，共18页。常用胆碱酯类药物乙酰胆碱（acetylcholine,ACh）醋甲胆碱（methacholine）卡巴胆碱（carbachol）贝胆碱（bethanechol）第三页，共18页。胆碱酯类药物共性季胺基团亲水性强，脂溶性差，不宜口服不易透过血脑屏障主要由乙酰胆碱酯酶水解，难易程度相差大激动M受体为主，空间选择性高，(S)-效能强于(R)-第四页，共18页。PropertiesofCommonlyUsedCholineEsterscholineestersusceptibilitytocholinesterasemuscarinicactionnicotinicactionacetylcholine++++++++++methacholine+++++nonecarbacholnegligible+++++bethanecholchloridenegligible++none第五页，共18页。乙酰胆碱(acetylcholine,ACh)药理作用

Bloodvesselsarteriesdilation(viaEDRF).

constriction(high-dosedirecteffect)

Heartsinoatrialnodedecreaseinrate(negativechronotropy)atriadecreaseincontractilestrength(negativeinotropy)

decreaseinrefractoryperiodatrioventricularnodedecreaseinconductionvelocity(negativedromotropy).increaseinrefractoryperiodventriclessmalldecreaseincontractilestrength第六页，共18页。药理作用：胃肠道、泌尿道gastrointestinaltract

motilityincreasesphinctersrelaxationsecretionstimulationurinarybladderdetrusorcontractiontrigoneandsphincterrelaxation

第七页，共18页。药理作用：其他glandssweat,salivary,lacrimal,

nasopharyngealsecretionEyesphinctermuscleofiriscontraction(miosis)ciliarymusclecontractionfornearvisionlungbronchialmusclecontraction(bronchoconstriction)bronchialglandsstimulation第八页，共18页。醋甲胆碱(methacholine)特点水解速度慢，作用时间较ACh长有muscarine样的作用，无nicotine样作用心血管系统作用明显用途口腔黏膜干燥症偶用于支气管高敏性的诊断禁忌证支气管哮喘、甲亢、冠状动脉缺血和溃疡病第九页，共18页。卡巴胆碱(carbachol)特点不易被AChE水解，作用时间长选择性差，对M、N胆碱受体均有激动作用对膀胱和肠道作用明显用途主要用于局部滴眼治疗青光眼术后腹气胀和尿潴留（皮下注射，禁用静注）*副作用较多，且atropine对它的解毒效果差第十页，共18页。贝胆碱(bethanechol)特点不易被AChE水解口服和注射均有效可兴奋胃肠道和泌尿道平滑肌，对心血管作用弱用途术后腹气胀、胃张力缺乏症及胃滞留等（bethanechol对M受体具有相对选择性，故其疗效较carbachol好）第十一页，共18页。-++++++++++++-pilocarpine-+++++++++++++-muscarine-++++++++++++--bethanechol+++++++++++++-carbachol+++++++++++++methacholine+++++++++++++++ACheye(topical)urinarybladdergastro-intestinalcardio-vascularnicotinicactivityantagonismbyatropinemuscarinicactivitysusceptibilitytocholinesterasemuscarinicagonistSomepharmacologicalpropertiesofcholineestersandnaturalalkaloids第十二页，共18页。生物碱类

(alkaloids)

第十三页，共18页。生物碱类(alkaloids)毛果芸香碱(pilocarpine)槟榔碱（arecoline）毒蕈碱(muscarine)震颤素(oxotremorine)第十四页，共18页。毛果芸香碱

(pilocarpine，匹鲁卡品)激动M受体缩瞳降低眼内压调节痉挛对眼的作用第十五页，共18页。毛果芸香碱

(pilocarpine，匹鲁卡品)

腺体

增加腺体分泌

平滑肌

兴奋肠道、支气管、子宫、膀胱、胆囊和胆道平滑肌

心血管系统

静脉注射pilocarpine0.1mg/kg，心率和血压短暂下降先用N受体阻断