十二章中樞神經(jīng)系統(tǒng)藥理學(xué)概論(09下)

十二章中樞神經(jīng)系統(tǒng)藥理學(xué)概論(09下)第一頁，共21頁。WelcomeMailboxforAnsweringQuestions答疑信箱

Website：Homepageofcampusnet/excellentcourses/Constructingcourses/Pharmacology

第二頁，共21頁。Chapter12中樞神經(jīng)系統(tǒng)藥理學(xué)概論目標(biāo)要求了解中樞神經(jīng)遞質(zhì)及其受體的代謝過程、生理功能了解中樞神經(jīng)系統(tǒng)藥物的分類及其特點(diǎn)。第三頁，共21頁。CNS:primaryconduction（主導(dǎo)）andcoordination（協(xié)調(diào)）Modes:nerveand/orhumoralregulation（神經(jīng)-體液調(diào)節(jié)）formaintaininghomeostasis（內(nèi)環(huán)境穩(wěn)態(tài)）andproducingresponseforexternalenvironment（外環(huán)境）Humans:dominatingintellectandcomplicatedbehaviors（主宰智能和復(fù)雜行為）第四頁，共21頁。1.Nervecell●Cellbody,dendrite（樹突）andaxon（軸突）●Inclusionbodyincytoplasm（胞漿內(nèi)含物）:pyknoticbody(致密小體)andlipofuscin(脂褐素)etc.●BasicstructureandfunctionunitofCNS●Majorfunction:transmittingmessage（傳遞信息）●Synapse（突觸）isthecentreoftransmittingmessageSection1CytologicBasisofCNSCNS的細(xì)胞學(xué)基礎(chǔ)第五頁，共21頁。2.Neuroglia（神經(jīng)膠質(zhì)細(xì)胞）Astrocyte（星形膠質(zhì)細(xì)胞）,oligodendrocyte（少突膠質(zhì)細(xì)胞）andmicroglia（小膠質(zhì)細(xì)胞）

Functions：support,insulation（絕緣）,homeostasis（內(nèi)環(huán)境穩(wěn)定）,guidingthegrowthofneuron（引導(dǎo)神經(jīng)元生長）,andparticipatingthedeactivationoftransmitter（遞質(zhì)滅活）andnerveregeneration（神經(jīng)再生）etc.第六頁，共21頁。3.Neuronalcircuit（神經(jīng)環(huán)路）Neuronregulationisperformedbyneuronalcircuit(notonlyoneneuron)Messagesareprocessedandintegratedbyneuroncircuit（神經(jīng)環(huán)路對(duì)信息進(jìn)行多種形式的處理和整合）第七頁，共21頁。4.SynapseandmessagetransmissionSynapsecomposition:presynapticmembrane前膜,postsynapticmembrane后膜andsynapticcleft間隙

Synapsecategories:chemical,electricandmixed

Synaptictransmission:synthesisandstorageoftransmitter,depolarizationofpresynapticmembraneandextracellularcalciuminfluxtriggeringtransmitterrelease,combinationoftransmitterandreceptorproducingbiologicaleffect,andtransmittereliminationandrecycletovesicle

信息可以在突觸部位進(jìn)行雙向傳遞第八頁，共21頁。Section2Transmitters（遞質(zhì)）andReceptorsofCNSNeurotransmitter:transmittingsignalquickly,strongactionandhighselectivity（傳遞信息快、作用強(qiáng)、選擇性高）Neuromodulator：不具遞質(zhì)活性，能調(diào)制遞質(zhì)的釋放和突觸后細(xì)胞的興奮性，作用慢、久、范圍廣Neurohormone:beingmainlyneuropeptides（神經(jīng)肽類）Severaltransmittersandmodulatorsmaycoexistinonenerveterminal（共存于同一神經(jīng)末稍）Someneurotrophic（神經(jīng)營養(yǎng)）andcellularfactors（細(xì)胞因子）impactinformationtransferbyregulatinggeneexpression第九頁，共21頁。Wehaveknownmorethan30transmitters.

1.Acetylcholine(ACh)

Distribution:widespreadinCNS

Receptors:M(especiallyM1)andN

Functions:involvinginmotion,memory,alertness（警覺）andinternalorganactivities（內(nèi)臟活動(dòng)）etc

Excitatorytransmitter（興奮性遞質(zhì)）,e.g.AChisreleasedinbrainwhenananimalisinfuriated（激怒）anditisreducedwhenananimalsleeps第十頁，共21頁。2.γ-aminobutyricacid(GABA)（γ氨基丁酸）

Widespreadandnon-uniform（廣泛非均勻）inbrain,especiallyinnigra(黑質(zhì))andglobuspallidus(蒼白球)Receptors:A,BandC,especiallyAtypeinbrainInhibitivetransmitter（抑制性遞質(zhì)）inCNS,e.g.GABAinsufficiencyofcerebralcortexinepilepticsmaycauseconvulsion;valproatesodiumcantreatvariouskindsofepilepticseizuresbecauseitinhibitsthedegradationofGABA（癲癇患者大腦皮層缺乏GABA可引起驚厥，丙戊酸鈉因能抑制GABA降解而對(duì)各種癲癇發(fā)作有效）第十一頁，共21頁。3.ExcitatoryAminoAcids(EAA)（興奮性氨基酸）

Glu（谷氨酸）andasp（天冬氨酸）:themaximalcontentaminoacidinmammal’brain（哺乳動(dòng)物腦內(nèi)含量最多的）Receptors:NMDA,AMPA,KAandmetabotropic（親代謝型）;theformerthreeareligand-gatedionchannel（配體門控離子通道）andthefinalimpactsphosphatidylinositol（磷脂酰肌醇）metabolismandadenylcyclase（腺苷酸環(huán)化酶）activityNMDAreceptoristhetargetofmanynervousandmentaldisordersEAAarerelatedwithstudyandmemory,neuronplasticity（神經(jīng)元可塑性）,epilepsy（癲癇）andCNSdegenerativediseases（中樞神經(jīng)系統(tǒng)退行性疾?。┑谑?，共21頁。4.Noradrenaline(NA)（去甲腎上腺素）ConcentrateddistributioninCNS,e.g.inhypothalamus（下丘腦）Receptors:αandβFunctions:alertness（警覺）,sleepandemotion（情緒）etc;e.g.whenNAneuronactivityincreases,happinessandagitationappear（當(dāng)中樞NA能神經(jīng)元活性增高時(shí)，表現(xiàn)愉快、激動(dòng)等效應(yīng)）.第十三頁，共21頁。5.Dopamine(DA)（多巴胺）Distribution:relativecentered;clearprojectionpathways;centeredinstriatum(ST,紋狀體),nigra(SN黑質(zhì))andglobuspallidus(蒼白球)SN－STpathway：錐體外系運(yùn)動(dòng)功能的高級(jí)中樞;function↓→PD,function↑→多動(dòng)癥Mes－limbic（中腦-邊緣）pathway:emotionandaffection（情緒和情感）Mes－cortex（中腦-皮層）pathway:cognition,thinking（思想）,sensationandsenses（理智）Tuberculum-funnel（結(jié)節(jié)-漏斗）pathway：調(diào)節(jié)垂體前葉的內(nèi)分泌功能第十四頁，共21頁。Receptors:D1andD2;fivesubtypesD1-5;thepharmacologicalcharacteristicsofD1andD5aresimilartothatofD1,whicharecalledD1-likereceptors（D1樣受體），theother—D2-likereceptors（D2樣受體）Relationswithdiseases：SN-STpathway↓→PD;treatment—supplementDAorDAreceptoragonists（激動(dòng)劑）中腦-邊緣和中腦-皮層通路D2樣受體功能亢進(jìn)致精神分裂癥，治療DA受體拮抗劑第十五頁，共21頁。6.5－Hydroxytryptamine(5－HT)（5-羥色胺）Distribution:similartothatofNA5-HTtransporter（轉(zhuǎn)運(yùn)體）isthemaintargetofantidepressants（抗抑郁藥）,參與心血管活動(dòng)、睡眠、痛覺、精神情感及內(nèi)分泌的調(diào)節(jié)。

Functions:inhibitionandstabilization（穩(wěn)定）

7.Histamine(H)（組胺）Maldistribution（分布不均）;多在下丘腦和網(wǎng)狀結(jié)構(gòu),H1,H2andH3receptorFunctions:regulatingpsychoactivity（精神活動(dòng)）,decreasingbodytemperature（體溫）,參與飲水和嘔吐;excitingH1→excitation,excitingH2→inhibition;抗組胺藥的嗜睡副作用可能與阻斷H1有關(guān)第十六頁，共21頁。8.EndopioidPeptide（內(nèi)阿片肽）MoreinSTandHT(下丘腦)Opium阿片hassedative（鎮(zhèn)靜）,hypnosis（催眠）,preventingcough（鎮(zhèn)咳）andinhibitingrespirationfunction（抑制呼吸）etc.9.Prostaglandin(PG)（前列腺素）Uniformitydistribution（均勻分布）,有致熱作用CentralPGsynthetase(cycloxygenase環(huán)氧酶)inhibitors,e.g.acetylsalicylicacid（乙酰水楊酸）reducesPGsothatithasantipyreticaction（解熱作用）第十七頁，共21頁。Section3CNS藥理學(xué)特點(diǎn)Excitation:自弱到強(qiáng)--欣快、失眠、不安、幻覺、妄想、躁狂和驚厥等。Inhibition:鎮(zhèn)靜、催眠、抑郁、麻醉、昏迷等.Drugcategories:中樞興奮藥和中樞抑制藥Inhibitionfunctionismoresensitiveto