药理学课件7-胆碱受体激动药

第7章胆碱受体激动药

Chapter7Cholinoceptoragonistscholinoceptoragonists

也称直接作用的拟胆碱药（direct-actingcholinomimeticdrugs）兴奋胆碱受体，发挥ACh样的作用乙酰胆碱(acetylcholine,ACh)theendogenousneurotransmitteratcholinergicsynapsesneuroeffectorjunctionsinthecentralandperipheralnervoussystemsactionsmediatedthroughcholinergicreceptorscholinergicreceptorsmuscariniccholinergicreceptors分布：autonomiceffectorcellsG蛋白偶联受体调节细胞内第二信使水平

nicotiniccholinergicreceptors分布：autonomicganglia&N-Mjunction离子通道受体第一节

M胆碱受体激动药

M胆碱受体激动药AcetylcholinereceptoragonistsarechemicalsthatrecognizeanddirectlybindtotheAChRsinthecentralandperipheralnervoussystems.ThesedrugsmimictheeffectsofAChandsocausemuscariniceffectsornicotiniceffectsintheperipheralandcentralnervoussystems.M胆碱受体激动药胆碱酯类(cholineesters)M、N受体均兴奋，但以M受体为主生物碱类(alkaloids)主要兴奋M胆碱受体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）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)-PropertiesofCommonlyUsedCholineEsterscholineestersusceptibilitytocholinesterasemuscarinicactionnicotinicactionacetylcholine++++++++++methacholine+++++nonecarbacholnegligible+++++bethanecholchloridenegligible++none乙酰胆碱

(acetylcholine,ACh)药理作用

心血管系统

血管扩张减慢心率减慢房室结和浦肯野纤维传导减弱心肌收缩力缩短心房不应期心脏离子通道药理作用：心血管系统Bloodvesselsarteriesdilation(viaEDRF).

constriction(high-dosedirecteffect)

Heartsinoatrialnodedecreaseinrate(negativechronotropy)atriadecreaseincontractilestrength(negativeinotropy)

decreaseinrefractoryperiodatrioventricularnodedecreaseinconductionvelocity(negativedromotropy).increaseinrefractoryperiodventriclessmalldecreaseincontractilestrength药理作用胃肠道

泌尿道

其他腺体眼神经节和骨骼肌中枢支气管药理作用：胃肠道、泌尿道gastrointestinaltract

motilityincreasesphinctersrelaxationsecretionstimulationurinarybladderdetrusorcontractiontrigoneandsphincterrelaxation

药理作用：其他glandssweat,salivary,lacrimal,

nasopharyngealsecretionEyesphinctermuscleofiriscontraction(miosis)ciliarymusclecontractionfornearvisionlungbronchialmusclecontraction(bronchoconstriction)bronchialglandsstimulation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）-++++++++++++-pilocarpine-+++++++++++++-muscarine-++++++++++++--bethanechol+++++++++++++-carbachol+++++++++++++methacholine+++++++++++++++ACheye(topical)urinarybladdergastro-intestinalcardio-vascularnicotinicactivityantagonismbyatropinemuscarinicactivitysusceptibilitytocholinesterasemuscarinicagonistSomepharmacologicalpropertiesofcholineestersandnaturalalkaloids生物碱类

(alkaloids)

生物碱类(alkaloids)毛果芸香碱(pilocarpine)槟榔碱（arecoline）毒蕈碱(muscarine)震颤素(oxotremorine)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受体阻断药，则pilocarpine可产生明显的升压作用上述两种作用均可被atropine所取消毛果芸香碱

(pilocarpine，匹鲁卡品)

临床用途

青光眼开角型闭角型虹膜炎（与扩瞳药交替使用）毒蕈碱

(muscarine)经典M胆碱受体激动药丝盖伞菌属和杯伞菌属含毒蕈碱成分毒蕈碱中毒症状表现：流涎、流泪、恶心、呕吐、头痛、视觉障碍、腹部绞