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pharmacology. General introduction Drugs acting on efferent nervous system Drugs acting on central nervous system Drugs acting on cardiovascular system Drugs acting on viscera Chemotherapeutic agents. Chapter 5 Intrduction to Pharmacology of Efferent Nervous System. Zhang Bin

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    1. pharmacology • General introduction • Drugs acting on efferent nervous system • Drugs acting on central nervous system • Drugs acting on cardiovascular system • Drugs acting on viscera • Chemotherapeutic agents

    2. Chapter 5 Intrduction to Pharmacologyof Efferent Nervous System Zhang Bin Institute of Pharmacology School of Medicine Shandong University

    3. Organization of Nervous system

    4. efferent nervous system (ENS) • autonomic nervous system (vegetative nervous system) • somatic motor nervous system

    5. Efferent neurons of the autonomic nervous system

    6. Classification of ENS according to the released neurotransmitters cholinergic nerve: acetylcholine (Ach) noradrenergic nerve: noradrenaline ( NA)

    7. Classification of ENS Central nervous system Ach skeletal muscle somatic motor nerve Ach NA Ach Ach sweat glands heart, vessel, smooth muscle sympathetic nerve Ach adrenal medulla AchAch glands, smooth muscle, heart Parasympathetic nerve

    8. Section 1 Neurotransmitter and Receptor of ENS • Neurotransmitter of ENS • The receptors of ENS

    9. 一. Neurotransmitter of ENS 1.Development of neurotransmitter theory • 100 years ago Chemical transmission electronic transmission • 1946 Von Euler NA (noradrenaline) • 1921 loewi double frog heart experiment • 1926 Dale Ach (acetylcholine)

    10. 2.Biosynthesis, storage, release and termination of neurotransmitters • Ach (acetylcholine) • NA (noradrenaline)

    11. inhibitor

    12. choline acetylase TH DD DH 2.Biosynthesis, storage, release and termination of neurotransmitters (1)Biosynthesis • choline + acetyl coenzymeA Ach • tyrosine dopa DA NA

    13. (2) Storage +ATP+protein store in vesicles Ach NA

    14. (3)release • exocytosis • quantal realease • cotransmission

    15. (4)Termination • Ach:acetylcholinesterase (AchE) in synapse • NA:uptake1 (neuronal uptake ) 75%-90% storage in vesicles\ MAO uptake2(non-neuronal uptake) COMT\MAO

    16. 二. The receptors of ENS Classification, Distribution and Effect

    17. Choline receptors (Cholinoceptors ) • M-R:muscarine • N-R: nicotine

    18. M-R: M1-R: ganglion, CNS M2-R: heart, presynaptic sites (negative feedback), CNS M3-R: exocrine glands, smooth muscle, endothelium, CNS M4 –R: exocrine glands, smooth muscle, CNS M5 -R: CNS Cholinoceptors

    19. Cholinoceptors N-R: nicotine NM-R: skeletal muscle NN-R: ganglion and CNS

    20. α-R α1-R: postsynaptic effector cells (especially smooth muscle) α2-R: presynaptic nerve terminals (negative feedback), platelet, smooth muscle, lipocytes adrenoceptor: NA AD

    21. adrenoceptor β-R • β1-R: postsynaptic effector cells, (especially heart, lipocytes,) presynaptic nerve terminals • β2-R: postsynaptic effector cells, (especially smooth muscle) • β3-R: postsynaptic effector cells, (especially lipocytes)

    22. Classification of receptor according to their structure • G-protein-coupled receptor: -R, -R, M-R, DA-R, 5-HT-R • Ligand-gated receptors N-R

    23. Structure of G-protein-coupled Receptor

    24. Molecular Mechanism of Gq-protein-coupled Receptor

    25. Molecular Mechanism of Gi/s-protein-coupled Receptor

    26. Structure of ligand-gated ion channel Receptor

    27. Molecular Mechanism of ligand-gated ion channel receptor

    28. 1. Cholinoceptors M-R: G-protein-coupled receptor M1-R:Gq-protein-coupled receptor M2-R-Gi-protein-coupled receptor N-R: ligand-gated ion channel receptor • 2.adrenoceptor:G-protein-coupled receptor α1 –R :Gq-protein-coupled receptor α2 –R: Gi-protein-coupled receptor β-R :Gs-protein-coupledreceptor

    29. (-) AC cAMP M2-R Gi K+,Ca2+ IP3 DAG Ca2+ (+)PKC M1-R Gq PLC α1-R PLC, PLA2, PLD Gq α2-R (-)AC cAMP (-)PKA Gi β-R Gs (+)AC cAMP (+)PKA Molecular Mechanism of Receptor G-protein-coupled receptor (-)PKA ligand-gated receptor : N-R Na +, K+,Ca2+

    30. terminology • adrenergic • adrenergic receptor • cholinergic • cholinergic receptor • postsynaptic receptor • presynaptic receptor

    31. Section 2The physiologicalactions of ENS • Co-innervation and Dominant Theory • Sympathetic actions: fight and flight response • Parasympathetic actions: rest and digest response

    32. Section 3 The basic mechanisms of actions of ENS drugs • 1.Direct action of receptors agonist blocker (antagonist) • 2.lnfluence of neurotransmitters biosynthesis release storage conversion

    33. Section 4 The classification of the ENS drugs

    34. (三)抗胆碱酯酶药

    35. Chapter 6 parasympathomimetics • Cholinoceptor agonists (cholinomimetics) • Anticholinesterase agents (cholinesterase-inhibiting drugs) • Drugs of enhancers of ACh release

    36. Cholinoceptor Agonists • M-R agonists: Choline esters: acetylcholine (ACh) alkaloids: pilocarpine • N-R agonists: nicotine

    37. Section 1 M-R agonists Acetylcholine (ACh) 1. unstable 2. low selectivity 3. administration route

    38. [Pharmacological actions] Directly activate M-R, N-R • muscarinic actions: small dose • nicotinic actions: large dose

    39. 1.muscarinic actions: small dose 1.cardiovascular system • vessel dilate a. NO release↑ (M3 R →EDRF(NO) ↑→GC →cGMP↑→ intracellular Ca2+↓) b. NA release↓ • BP (HR) • Heart depress: negative (chronotropic, dromotropic, inotropic) effect

    40. 1.muscarinic actions: small dose 2.glands ↑ 3.gastrointestinal tract: motility increase, secretion stimulation 4. urinary bladder: detrusor muscle (逼尿肌)contraction, trigone and sphincter relaxation 5.eye: sphincter muscle of iris (虹膜) contract: miosis ciliary muscle contract: near vision

    41. 2.nicotinic actions:large dose • NN-R: dominant nerve actions • NM-R:skeletal muscle contraction

    42. alkaloids • Pilocarpine(毛果芸香碱,匹鲁卡品) • Muscarine(毒蕈碱) • Arecoline(槟榔碱) • Oxotremorine(氧化震颤素)

    43. Pilocarpine Pharmacological actions: selectively activate M-R 1.Eye • miosis : pupiliary sphincter • decrease intraocular pressure • spasm of accommadation : ciliary muscle