十二章中枢神经系统药理学概论(09下)

十二章中枢神经系统药理学概论(09下)第一页，共21页。WelcomeMailboxforAnsweringQuestions答疑信箱

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第二页，共21页。Chapter12中枢神经系统药理学概论目标要求了解中枢神经递质及其受体的代谢过程、生理功能了解中枢神经系统药物的分类及其特点。第三页，共21页。CNS:primaryconduction（主导）andcoordination（协调）Modes:nerveand/orhumoralregulation（神经-体液调节）formaintaininghomeostasis（内环境稳态）andproducingresponseforexternalenvironment（外环境）Humans:dominatingintellectandcomplicatedbehaviors（主宰智能和复杂行为）第四页，共21页。1.Nervecell●Cellbody,dendrite（树突）andaxon（轴突）●Inclusionbodyincytoplasm（胞浆内含物）:pyknoticbody(致密小体)andlipofuscin(脂褐素)etc.●BasicstructureandfunctionunitofCNS●Majorfunction:transmittingmessage（传递信息）●Synapse（突触）isthecentreoftransmittingmessageSection1CytologicBasisofCNSCNS的细胞学基础第五页，共21页。2.Neuroglia（神经胶质细胞）Astrocyte（星形胶质细胞）,oligodendrocyte（少突胶质细胞）andmicroglia（小胶质细胞）

Functions：support,insulation（绝缘）,homeostasis（内环境稳定）,guidingthegrowthofneuron（引导神经元生长）,andparticipatingthedeactivationoftransmitter（递质灭活）andnerveregeneration（神经再生）etc.第六页，共21页。3.Neuronalcircuit（神经环路）Neuronregulationisperformedbyneuronalcircuit(notonlyoneneuron)Messagesareprocessedandintegratedbyneuroncircuit（神经环路对信息进行多种形式的处理和整合）第七页，共21页。4.SynapseandmessagetransmissionSynapsecomposition:presynapticmembrane前膜,postsynapticmembrane后膜andsynapticcleft间隙

Synapsecategories:chemical,electricandmixed

Synaptictransmission:synthesisandstorageoftransmitter,depolarizationofpresynapticmembraneandextracellularcalciuminfluxtriggeringtransmitterrelease,combinationoftransmitterandreceptorproducingbiologicaleffect,andtransmittereliminationandrecycletovesicle

信息可以在突触部位进行双向传递第八页，共21页。Section2Transmitters（递质）andReceptorsofCNSNeurotransmitter:transmittingsignalquickly,strongactionandhighselectivity（传递信息快、作用强、选择性高）Neuromodulator：不具递质活性，能调制递质的释放和突触后细胞的兴奋性，作用慢、久、范围广Neurohormone:beingmainlyneuropeptides（神经肽类）Severaltransmittersandmodulatorsmaycoexistinonenerveterminal（共存于同一神经末稍）Someneurotrophic（神经营养）andcellularfactors（细胞因子）impactinformationtransferbyregulatinggeneexpression第九页，共21页。Wehaveknownmorethan30transmitters.

1.Acetylcholine(ACh)

Distribution:widespreadinCNS

Receptors:M(especiallyM1)andN

Functions:involvinginmotion,memory,alertness（警觉）andinternalorganactivities（内脏活动）etc

Excitatorytransmitter（兴奋性递质）,e.g.AChisreleasedinbrainwhenananimalisinfuriated（激怒）anditisreducedwhenananimalsleeps第十页，共21页。2.γ-aminobutyricacid(GABA)（γ氨基丁酸）

Widespreadandnon-uniform（广泛非均匀）inbrain,especiallyinnigra(黑质)andglobuspallidus(苍白球)Receptors:A,BandC,especiallyAtypeinbrainInhibitivetransmitter（抑制性递质）inCNS,e.g.GABAinsufficiencyofcerebralcortexinepilepticsmaycauseconvulsion;valproatesodiumcantreatvariouskindsofepilepticseizuresbecauseitinhibitsthedegradationofGABA（癫痫患者大脑皮层缺乏GABA可引起惊厥，丙戊酸钠因能抑制GABA降解而对各种癫痫发作有效）第十一页，共21页。3.ExcitatoryAminoAcids(EAA)（兴奋性氨基酸）

Glu（谷氨酸）andasp（天冬氨酸）:themaximalcontentaminoacidinmammal’brain（哺乳动物脑内含量最多的）Receptors:NMDA,AMPA,KAandmetabotropic（亲代谢型）;theformerthreeareligand-gatedionchannel（配体门控离子通道）andthefinalimpactsphosphatidylinositol（磷脂酰肌醇）metabolismandadenylcyclase（腺苷酸环化酶）activityNMDAreceptoristhetargetofmanynervousandmentaldisordersEAAarerelatedwithstudyandmemory,neuronplasticity（神经元可塑性）,epilepsy（癫痫）andCNSdegenerativediseases（中枢神经系统退行性疾病）第十二页，共21页。4.Noradrenaline(NA)（去甲肾上腺素）ConcentrateddistributioninCNS,e.g.inhypothalamus（下丘脑）Receptors:αandβFunctions:alertness（警觉）,sleepandemotion（情绪）etc;e.g.whenNAneuronactivityincreases,happinessandagitationappear（当中枢NA能神经元活性增高时，表现愉快、激动等效应）.第十三页，共21页。5.Dopamine(DA)（多巴胺）Distribution:relativecentered;clearprojectionpathways;centeredinstriatum(ST,纹状体),nigra(SN黑质)andglobuspallidus(苍白球)SN－STpathway：锥体外系运动功能的高级中枢;function↓→PD,function↑→多动症Mes－limbic（中脑-边缘）pathway:emotionandaffection（情绪和情感）Mes－cortex（中脑-皮层）pathway:cognition,thinking（思想）,sensationandsenses（理智）Tuberculum-funnel（结节-漏斗）pathway：调节垂体前叶的内分泌功能第十四页，共21页。Receptors:D1andD2;fivesubtypesD1-5;thepharmacologicalcharacteristicsofD1andD5aresimilartothatofD1,whicharecalledD1-likereceptors（D1样受体），theother—D2-likereceptors（D2样受体）Relationswithdiseases：SN-STpathway↓→PD;treatment—supplementDAorDAreceptoragonists（激动剂）中脑-边缘和中脑-皮层通路D2样受体功能亢进致精神分裂症，治疗DA受体拮抗剂第十五页，共21页。6.5－Hydroxytryptamine(5－HT)（5-羟色胺）Distribution:similartothatofNA5-HTtransporter（转运体）isthemaintargetofantidepressants（抗抑郁药）,参与心血管活动、睡眠、痛觉、精神情感及内分泌的调节。

Functions:inhibitionandstabilization（稳定）

7.Histamine(H)（组胺）Maldistribution（分布不均）;多在下丘脑和网状结构,H1,H2andH3receptorFunctions:regulatingpsychoactivity（精神活动）,decreasingbodytemperature（体温）,参与饮水和呕吐;excitingH1→excitation,excitingH2→inhibition;抗组胺药的嗜睡副作用可能与阻断H1有关第十六页，共21页。8.EndopioidPeptide（内阿片肽）MoreinSTandHT(下丘脑)Opium阿片hassedative（镇静）,hypnosis（催眠）,preventingcough（镇咳）andinhibitingrespirationfunction（抑制呼吸）etc.9.Prostaglandin(PG)（前列腺素）Uniformitydistribution（均匀分布）,有致热作用CentralPGsynthetase(cycloxygenase环氧酶)inhibitors,e.g.acetylsalicylicacid（乙酰水杨酸）reducesPGsothatithasantipyreticaction（解热作用）第十七页，共21页。Section3CNS药理学特点Excitation:自弱到强--欣快、失眠、不安、幻觉、妄想、躁狂和惊厥等。Inhibition:镇静、催眠、抑郁、麻醉、昏迷等.Drugcategories:中枢兴奋药和中枢抑制药Inhibitionfunctionismoresensitiveto