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1、Department of Pharmacology(药理学) Hubei Medical University,Drugs for Central Nervous System 中 枢 神 经 系 统 药 物,Wanhong Zhao (赵万红),Welcome,Mailbox for Answering Questions 答疑信箱 Website：Homepage of campus net/excellent courses/Constructing courses/Pharmacology ,Chapter 12 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、
2、生理功能 了解中枢神经系统药物的分类及其特点。,CNS:primary conduction（主导）and coordination（协调） Modes:nerve and/or humoral regulation（神经-体液调节） for maintaining homeostasis（内环境稳态） and producing response for external environment（外环境） Humans:dominating intellect and complicated behaviors（主宰智能和复杂行为）,1.Nerve cell Cell body, dendr
3、ite（树突） and axon（轴突） Inclusion body in cytoplasm（胞浆内含物）: pyknotic body(致密小体) and lipofuscin(脂褐素) etc. Basic structure and function unit of CNS Major function: transmitting message（传递信息） Synapse（突触） is the centre of transmitting message,Section 1 Cytologic Basis of CNS CNS的细胞学基础,2. Neuroglia（神经胶质细胞）,
4、Astrocyte（星形胶质细胞）, oligodendrocyte（少突胶质细胞） and microglia（小胶质细胞） Functions：support, insulation（绝缘）, homeostasis（内环境稳定）, guiding the growth of neuron（引导神经元生长）, and participating the deactivation of transmitter（递质灭活） and nerve regeneration（神经再生） etc.,3. Neuronal circuit（神经环路）,Neuron regulation is perfo
5、rmed by neuronal circuit (not only one neuron) Messages are processed and integrated by neuron circuit（神经环路对信息进行多种形式的处理和整合）,4. Synapse and message transmission,Synapse composition: presynaptic membrane前膜, postsynaptic membrane后膜and synaptic cleft间隙 Synapse categories: chemical, electric and mixed Sy
6、naptic transmission: synthesis and storage of transmitter, depolarization of presynaptic membrane and extracellular calcium influx triggering transmitter release, combination of transmitter and receptor producing biological effect, and transmitter elimination and recycle to vesicle 信息可以在突触部位进行双向传递,S
7、ection 2 Transmitters（递质） and Receptors of CNS,Neurotransmitter: transmitting signal quickly, strong action and high selectivity（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: being mainly neuropeptides（神经肽类） Several transmitters and modulators may coexist in one ne
8、rve terminal（共存于同一神经末稍） Some neurotrophic（神经营养） and cellular factors（细胞因子） impact information transfer by regulating gene expression,We have known more than 30 transmitters. 1. Acetylcholine (ACh) Distribution: widespread in CNS Receptors: M (especially M1) and N Functions: involving in motion, memo
9、ry, alertness（警觉） and internal organ activities（内脏活动） etc Excitatory transmitter（兴奋性递质）, e.g. ACh is released in brain when an animal is infuriated（激怒） and it is reduced when an animal sleeps,2. -aminobutyric acid (GABA) （氨基丁酸） Widespread and non-uniform（广泛非均匀） in brain, especially in nigra (黑质) and
10、 globus pallidus (苍白球) Receptors: A, B and C, especially A type in brain Inhibitive transmitter（抑制性递质） in CNS, e.g. GABA insufficiency of cerebral cortex in epileptics may cause convulsion; valproate sodium can treat various kinds of epileptic seizures because it inhibits the degradation of GABA（癫痫患
11、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）,3. Excitatory Amino Acids (EAA)（兴奋性氨基酸） Glu（谷氨酸） and asp（天冬氨酸）: the maximal content amino acid in mammal brain（哺乳动物脑内含量最多的） Receptors: NMDA, AMPA, KA and metabotropic（亲代谢型）; the former three are ligand-gated ion channel（配体门控离子通道） and the final impacts phosp
12、hatidylinositol（磷脂酰肌醇） metabolism and adenylcyclase（腺苷酸环化酶） activity NMDA receptor is the target of many nervous and mental disorders EAA are related with study and memory, neuron plasticity（神经元可塑性）, epilepsy（癫痫） and CNS degenerative diseases（中枢神经系统退行性疾病）,4. Noradrenaline (NA)（去甲肾上腺素） Concentrated d
13、istribution in CNS, e.g. in hypothalamus（下丘脑） Receptors: and Functions: alertness（警觉）, sleep and emotion（情绪） etc; e.g. when NA neuron activity increases, happiness and agitation appear（当中枢NA能神经元活性增高时，表现愉快、激动等效应）.,5. Dopamine (DA)（多巴胺） Distribution : relative centered; clear projection pathways; cent
14、ered in striatum (ST, 纹状体), nigra (SN黑质) and globus pallidus (苍白球) SNST pathway：锥体外系运动功能的高级中枢; function PD, function 多动症 Meslimbic（中脑-边缘） pathway : emotion and affection（情绪和情感） Mescortex（中脑-皮层） pathway: cognition, thinking（思想）, sensation and senses（理智） Tuberculum-funnel（结节-漏斗） pathway：调节垂体前叶的内分泌功能,R
15、eceptors: D1 and D2; five subtypes D1-5; the pharmacological characteristics of D1 and D5 are similar to that of D1, which are called D1-like receptors（D1样受体），the otherD2-like receptors（D2样受体） Relations with diseases： SN-ST pathway PD; treatmentsupplement DA or DA receptor agonists（激动剂） 中脑-边缘和中脑-皮层通
16、路D2样受体功能亢进致精神分裂症，治疗DA受体拮抗剂,6. 5Hydroxytryptamine (5HT)（5-羟色胺） Distribution: similar to that of NA 5-HT transporter（转运体） is the main target of antidepressants（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: inhibition and stabilization（稳定） 7. Histamine (H)（组胺） Maldistribution（分布不均）; 多在下丘脑和网状结构, H1, H2 and H3 receptor Functions: regulating psychoactivity（精神活动）, decreasing body temperature（体温）, 参与饮水和呕吐; exciting H1excitation, exciting H2inhibition;抗组胺药的嗜
