第7章膽堿受體激動藥

Chapter7Cholinoceptoragonistscholinoceptoragonists

也稱直接作用的擬膽堿藥（direct-actingcholinomimeticdrugs）興奮膽堿受體，發(fā)揮ACh樣的作用乙酰膽堿(acetylcholine,ACh)theendogenousneurotransmitteratcholinergicsynapsesneuroeffectorjunctionsinthecentralandperipheralnervoussystemsactionsmediatedthroughcholinergicreceptorscholinergicreceptorsmuscariniccholinergicreceptors分布：autonomiceffectorcellsG蛋白偶聯(lián)受體調(diào)節(jié)細胞內(nèi)第二信使水平

nicotiniccholinergicreceptors分布：autonomicganglia&N-Mjunction離子通道受體第一節(jié)

M膽堿受體激動藥

M膽堿受體激動藥AcetylcholinereceptoragonistsarechemicalsthatrecognizeanddirectlybindtotheAChRsinthecentralandperipheralnervoussystems.ThesedrugsmimictheeffectsofAChandsocausemuscariniceffectsornicotiniceffectsintheperipheralandcentralnervoussystems.M膽堿受體激動藥膽堿酯類(cholineesters)M、N受體均興奮，但以M受體為主生物堿類(alkaloids)主要興奮M膽堿受體常用膽堿酯類藥物乙酰膽堿（acetylcholine,ACh）醋甲膽堿（methacholine）卡巴膽堿（carbachol）貝膽堿（bethanechol）膽堿酯類藥物共性季胺基團親水性強，脂溶性差，不宜口服不易透過血腦屏障主要由乙酰膽堿酯酶水解，難易程度相差大激動M受體為主，空間選擇性高，(S)-效能強于(R)-PropertiesofCommonlyUsedCholineEsterscholineestersusceptibilitytocholinesterasemuscarinicactionnicotinicactionacetylcholine++++++++++methacholine+++++nonecarbacholnegligible+++++bethanecholchloridenegligible++none乙酰膽堿

(acetylcholine,ACh)藥理作用

心血管系統(tǒng)

血管擴張減慢心率減慢房室結(jié)和浦肯野纖維傳導(dǎo)減弱心肌收縮力縮短心房不應(yīng)期心臟離子通道藥理作用：心血管系統(tǒng)Bloodvesselsarteriesdilation(viaEDRF).

constriction(high-dosedirecteffect)

Heartsinoatrialnodedecreaseinrate(negativechronotropy)atriadecreaseincontractilestrength(negativeinotropy)

decreaseinrefractoryperiodatrioventricularnodedecreaseinconductionvelocity(negativedromotropy).increaseinrefractoryperiodventriclessmalldecreaseincontractilestrength藥理作用胃腸道

泌尿道

其他腺體眼神經(jīng)節(jié)和骨骼肌中樞支氣管藥理作用：胃腸道、泌尿道gastrointestinaltract

motilityincreasesphinctersrelaxationsecretionstimulationurinarybladderdetrusorcontractiontrigoneandsphincterrelaxation

藥理作用：其他glandssweat,salivary,lacrimal,

nasopharyngealsecretionEyesphinctermuscleofiriscontraction(miosis)ciliarymusclecontractionfornearvisionlungbronchialmusclecontraction(bronchoconstriction)bronchialglandsstimulation醋甲膽堿(methacholine)特點水解速度慢，作用時間較ACh長有muscarine樣的作用，無nicotine樣作用心血管系統(tǒng)作用明顯用途口腔黏膜干燥癥偶用于支氣管高敏性的診斷禁忌證支氣管哮喘、甲亢、冠狀動脈缺血和潰瘍病卡巴膽堿(carbachol)特點不易被AChE水解，作用時間長選擇性差，對M、N膽堿受體均有激動作用對膀胱和腸道作用明顯用途主要用于局部滴眼治療青光眼術(shù)后腹氣脹和尿潴留（皮下注射，禁用靜注）*副作用較多，且atropine對它的解毒效果差貝膽堿(bethanechol)特點不易被AChE水解口服和注射均有效可興奮胃腸道和泌尿道平滑肌，對心血管作用弱用途術(shù)后腹氣脹、胃張力缺乏癥及胃滯留等（bethanechol對M受體具有相對選擇性，故其療效較carbachol好）-++++++++++++-pilocarpine-+++++++++++++-muscarine-++++++++++++--bethanechol+++++++++++++-carbachol+++++++++++++methacholine+++++++++++++++ACheye(topical)urinarybladdergastro-intestinalcardio-vascularnicotinicactivityantagonismbyatropinemuscarinicactivitysusceptibilitytocholinesterasemuscarinicagonistSomepharmacologicalpropertiesofcholineestersandnaturalalkaloids生物堿類

(alkaloids)

生物堿類(alkaloids)毛果蕓香堿(pilocarpine)檳榔堿（arecoline）毒蕈堿(muscarine)震顫素(oxotremorine)毛果蕓香堿

(pilocarpine，匹魯卡品)激動M受體縮瞳降低眼內(nèi)壓調(diào)節(jié)痙攣

對眼的作用毛果蕓香堿

(pilocarpine，匹魯卡品)

腺體

增加腺體分泌

平滑肌

興奮腸道、支氣管、子宮、膀胱、膽囊和膽道平滑肌

心血管系統(tǒng)

靜脈注射pilocarpine0.1mg/kg，心率和血壓短暫下降先用N受體阻斷藥，則pilocarpine可產(chǎn)生明顯的升壓作用上述兩種作用均可被atropine所取消毛果蕓香堿

(pilocarpine，匹魯卡品)

臨床用途

青光眼開角型閉角型虹膜炎（與擴瞳藥交替使用）毒蕈堿

(muscarine)經(jīng)典M膽堿受體激動藥絲蓋傘菌屬和杯傘菌屬含毒蕈堿成分毒蕈堿中毒癥狀表現(xiàn)：流涎、流淚、惡心、嘔吐、頭痛、視覺障礙、腹部絞