autonomic pharmacology 张纬萍浙江大学医学院药理 [email protected] 2013.10.11






EfferentEfferentDivisionDivision

AfferentAfferentDivisionDivision









Somatic motorSomatic motorNervous SystemNervous System









Autonomic nervousAutonomic nervousSystem (ANS)System (ANS)



Sympathetic Sympathetic 交感交感








ParasympatheticParasympathetic 副交感副交感

Enteric Enteric 肠神经系统肠神经系统神经系统神经系统



交感和副交感神经系统交感和副交感神经系统

thoracolumbarthoracolumbarcraniosacralcraniosacral

The Enteric Nervous SystemThe Enteric Nervous System 肠神经系统肠神经系统 (+SNS/PSNS)(+SNS/PSNS)

Circular muscle layer环行肌

longitudinal muscle layer纵行肌

Absorptive cell吸收细胞

Enterochromaffin cell肠噬铬细胞

Submucosal plexus粘膜下神经丛

Myenteric plexus肌间神经丛

Secretory cell分泌细胞

The release of noradrenaline has the following effects

stimulates heartbeat raises blood pressure dilates the pupils dilates the trachea and bronchi stimulates the conversion of liver glycogen into

glucose shunts blood away from the skin and viscera to the

skeletal muscles, brain, and heart inhibits peristalsis in the gastrointestinal (GI) tract inhibits contraction of the bladder and rectum

Parasympathetic stimulation causes

slowing down of the heartbeat

lowering of blood pressure

constriction of the pupils

increased blood flow to the skin and viscera

peristalsis of the GI tract


SympatheticSympathetic








ParasympatheticParasympathetic

(Enteric)(Enteric)

Drugs that produce their primary

therapeutic effect by mimicking or

altering the functions of autonomic

nervous system are called

autonomic drugs.



NeurotransmittersNeurotransmitters

ReceptorsReceptors

drugs

NeurotransmittersNeurotransmitters•SynthesisSynthesis•StorageStorage•ReleaseRelease•InactivationInactivation

ReceptorsReceptors•ActivationActivation

ReceptorsReceptors

drugsDirect actions Direct actions

AgonistsAgonists 激动剂激动剂

AntagonistsAntagonists拮抗剂拮抗剂


Synthesis Synthesis Transport and storageTransport and storage Release Release InactivationInactivation

Indirect actions Indirect actions

Direct-acting: receptor agonistsDirect-acting: receptor agonists Indirect-acting: increasing Indirect-acting: increasing

amounts and/or effects of amounts and/or effects of transmitterstransmitters

Direct-acting: receptorDirect-acting: receptor antagonistsantagonists Indirect-acting: decreasing Indirect-acting: decreasing


MimeticsMimetics

AntagonistsAntagonists

ReceptorsReceptors


AgonistsAgonists 激动剂激动剂

AntagonistsAntagonists拮抗剂拮抗剂


Synthesis Synthesis Transport and storageTransport and storage Release Release InactivationInactivation


Direct-acting:Direct-acting: receptor agonists receptor agonists Indirect-acting:Indirect-acting: increasing increasing


Direct-acting:Direct-acting: receptor receptor antagonistsantagonists Indirect-acting:Indirect-acting: decreasing decreasing


MimeticsMimetics

AntagonistsAntagonists

Cholinergic PharmacologyCholinergic PharmacologyAdrenergic PharmacologyAdrenergic Pharmacology

1.1. Choline UptakeCholine Uptake

2.2. ACh SynthesisACh SynthesisCholine Choline

acetyltransferase(ChAT)acetyltransferase(ChAT)Choline + AcCoA → ACh Choline + AcCoA → ACh ChATChAT

3.3. ACh StorageACh Storage

4.4. ACh ReleaseACh Release

5.5. ACh EffectsACh Effectsa)a) PostsynapticPostsynapticb)b) PresynapticPresynaptic

6.6. ACh MetabolismACh MetabolismAcetylcholinesterase(AChE)Acetylcholinesterase(AChE) AChACh → Choline + Acetate→ Choline + Acetate AChEAChE

Cholinergic TerminalCholinergic Terminal

RegulationRegulation

- by auto-receptors- by auto-receptorsACh acting on presynaptic MACh acting on presynaptic M22-cholinergic receptors-cholinergic receptors

- by hetero-receptors- by hetero-receptorsNE acting on presynaptic NE acting on presynaptic 22-adrenergic receptors-adrenergic receptors

- by metabolism (extra-neuronal)- by metabolism (extra-neuronal)

Acetylcholine Releaseby exocytosis

Cholinesterases胆碱酯酶

AcetylcholinesteraseAcetylcholinesterase is located at cholinergic synapses is located at cholinergic synapses and in erythrocytes and in erythrocytes (does not (does not hydrolyze succinylcholine)hydrolyze succinylcholine)

PseudocholinesterasePseudocholinesterase ((假性胆碱酯酶，假性胆碱酯酶， synonyms: plasma synonyms: plasma cholinesterase or butyrylcholinesterasecholinesterase or butyrylcholinesterase丁酰胆碱酯酶丁酰胆碱酯酶 )) exists mainly in plasma, liver and in glia exists mainly in plasma, liver and in glia ((hydrolyzes hydrolyzes succinylcholine)succinylcholine)

CholinergicCholinergic Receptors Receptors

(cholinoceptors, acetylcholine receptors)(cholinoceptors, acetylcholine receptors)

Muscarinic receptors (M receptors)Muscarinic receptors (M receptors) MM1, 3, 51, 3, 5 ; M ; M2, 42, 4

G-protein Coupled End Organs

Nicotinic receptors (N receptors)Nicotinic receptors (N receptors) NNNN (N (N11) receptors; N) receptors; NMM(N(N2 2 )) receptorsreceptors Ligand-gated Ion Channels NMJ & Ganglia

M receptors : M receptors : G-protein G-protein CoupledCoupled

MuscarinicMuscarinicReceptorReceptorSignalingSignalingPathwaysPathways

SmoothMusclecontraction

cAMP↓

Heart rate↓

(first, (first, second, second, third messenger)third messenger)

The response of an isolated blood vessel to ACh depends on whether the endothelium is intact (unrubbed) or missing

When the endothelium is present, ACh causes smooth muscle relaxation by stimulating the production of nitric oxide (NO) in the endothelium

In the absence of the endothelium, a small amount of vasoconstriction is observed ——Fred Murad, 1998

M receptors : end organs and effect of activationM receptors : end organs and effect of activation

血管平滑肌血管平滑肌：收缩或舒张：收缩或舒张

心脏：心脏： Depression of the heart Depression of the heart

— — 负性肌力：负性肌力： NENE 释放释放— — 负性频率：负性频率： open Kopen K++ channel channel ，， depolarizationdepolarization

— — 负性传导：负性传导： AV node and Purkinje fibersAV node and Purkinje fibers

— — 缩短心房不应期：缩短心房不应期： AP durationAP duration


平滑肌：平滑肌：收缩收缩 (sensitive:sensitive: GI tract, bronchial, GI tract, bronchial, urinary bladder;urinary bladder; insensitive:insensitive: uterine, blood uterine, blood vascular) vascular) Mostly smooth muscle contraction - heart being the main exception

外分泌腺：外分泌腺： sensitive: sensitive: sweat, tears, salivary; sweat, tears, salivary; insensitive: insensitive: GI tract;GI tract;

Eye Eye (contraction of sphincter muscle of iris: (contraction of sphincter muscle of iris: miosismiosis 缩瞳缩瞳 ; contraction of ciliary muscle; contraction of ciliary muscle 睫状睫状肌收缩肌收缩 : : contraction for near visioncontraction for near vision))

CNSCNS: activation: activation ，， yet ACh can hardly pass yet ACh can hardly pass BBBBBB


NNNN receptors receptors （（ NN11 receptors receptors ）） Sympathetic and parasympathetic gangliaSympathetic and parasympathetic ganglia

Adrenal medullaAdrenal medulla

NNMM receptors receptors （（ NN2 2 receptors receptors ）） The Neuromuscular Junction (NMJ) The Neuromuscular Junction (NMJ)

(Contraction of skeletal muscles)(Contraction of skeletal muscles)

N receptors : subtypes and locationN receptors : subtypes and location

N receptors : N receptors : Ligand-gated Ion ChannelsLigand-gated Ion Channels

• At the NMJ, At the NMJ, N receptorsN receptors Pentameric with four Pentameric with four types of subunits, two types of subunits, two subunits bind ACh for subunits bind ACh for ligand gatingligand gating

• All other All other nAChRs, nAChRs, including those including those at the at the peripheral peripheral ganglia, have 2 ganglia, have 2 ’s and 3 ’s and 3 ’s’s

The Neuromuscular The Neuromuscular

Junction (NMJ)Junction (NMJ)

AA BB

Myasthenia GravisMyasthenia Gravis 重症肌无力重症肌无力 This means This means ““serious disorder the NMJserious disorder the NMJ””

This is an autoimmune diseaseThis is an autoimmune disease

Antibodies against the Antibodies against the subunit of the nAChR subunit of the nAChR

The ability of ACh to activate the nAChRs is The ability of ACh to activate the nAChRs is blocked by the antibodiesblocked by the antibodies

As for many autoimmune diseases, stress can As for many autoimmune diseases, stress can make the symptoms worsemake the symptoms worse

Treatment is to potentiate cholinergic signaling Treatment is to potentiate cholinergic signaling and to remove the antibodies (blood dialysis)and to remove the antibodies (blood dialysis)

M- and N- ReceptorsM- and N- Receptors


Cholinoceptor agonistsCholinoceptor agonistsM, N receptor agonists:M, N receptor agonists: acetylcholineacetylcholine ，乙酰胆碱，乙酰胆碱M receptor agonists:M receptor agonists: pilocarpinepilocarpine ，匹鲁卡品，匹鲁卡品N receptor agonists:N receptor agonists: nicotinenicotine ，尼古丁，尼古丁

AChAChCholinesterase inhibitors Cholinesterase inhibitors (Anticholinesterases)(Anticholinesterases)Reversible: neostigmineReversible: neostigmine 新斯的明新斯的明Irreversible: organophosphatesIrreversible: organophosphates


Cholinergic antagonistsCholinergic antagonists

Drug classificationDrug classification

Cholinomimetics:Cholinomimetics:Direct-acting drugsDirect-acting drugs

AChEAChEResistantResistant

AChAChDerivativesDerivatives Bond

cleaved by AChE

乙酰胆碱

乙酰甲胆碱

卡巴胆碱

氯贝胆碱

BethanecholBethanechol is most commonly used, particularly post- is most commonly used, particularly post-operation for the treatment of paralytic ileusoperation for the treatment of paralytic ileus （麻痹性肠梗（麻痹性肠梗阻）阻） and urinary retentionand urinary retention （尿储留）（尿储留）

Cholinomimetics:Cholinomimetics:Direct-acting drugsDirect-acting drugs

Natural Muscarinic AgonistsNatural Muscarinic Agonists

(Most to least nicotinic)(Most to least nicotinic)

匹鲁卡品毛果云香硷槟榔碱

毒蕈碱

amanita muscaria(mushroom)

pilocarpus (S. Amer. shrub)

areca or betal nuts (India,E. Indies)

Atropa belladonna => atropineAmanita muscaria => muscarine

““Food” PoisoningFood” Poisoning

Deadly Nightshade, 癫茄

Pilocarpus=> Pilocarpine Areca nuts=> Arecoline

Poisoning causes muscarinic overstimulation

or blocking (for belladonna only)

- salivation, lacrimation(流泪 ), visual

disturbances;

- abdominal colic and diarrhea

- bronchospasm and bradycardia

- hypotension; shock

Treatment is with atropine

““Food” PoisoningFood” Poisoning

Muscarinic Agonists:Muscarinic Agonists: Parasympathetic Effects & Therapeutic Uses Parasympathetic Effects & Therapeutic Uses

PilocarpinePilocarpine（（ 11 ）） EyesEyes • Miosis(Miosis( 缩瞳缩瞳 ): ): contraction of sphincter muscle of iris• Lowing intraocular pressure:Lowing intraocular pressure: enlarging angle of anterior

chamber, increasing drainage of aqueous humor• Spasm of accommodation(Spasm of accommodation( 调节痉挛调节痉挛 ): ): contraction of

ciliary muscle, contraction for near vision

Ophthalmological usesOphthalmological uses Glaucoma(Glaucoma( 青光眼青光眼 ):): (concentration (concentration ≤ ≤ 2%)2%) narrow (closed)- narrow (closed)- oror wide (open)-angleswide (open)-angles it is the drug of choice in the emergency lowering of intraocular pressureit is the drug of choice in the emergency lowering of intraocular pressure Iritis (Iritis ( 虹膜炎虹膜炎 ):): mioticsmiotics（缩瞳）（缩瞳） /mydriatics/mydriatics （扩瞳）（扩瞳）

light

睫状肌

巩膜窦

睫状体上皮细胞

小梁网

pilocarpinepilocarpine

atropineatropine lenslens

miosismiosis

mydriasismydriasis

paralysis of paralysis of accommodationaccommodation

near sightnear sight

spasm of spasm of accommodationaccommodation

far sightfar sight

irisiris

Anterior Anterior chamberchamber

Ciliary muscleCiliary muscle (contraction)(contraction)

zonulezonule

Anterior Anterior chamberchamber

zonulezonule

Canal of SchlemmCanal of Schlemm

posteriorposteriorchamberchamber

Ciliary muscleCiliary muscle (dilation)(dilation)

悬韧带

Glaucoma• Disease of the aging eye -

increased intraocular pressure (IOP), degeneration of the optic head, and restricted visual field typify primary open-angle glaucoma

• obstruction of the aqueous drainage leads to elevated IOP, and may result in glaucomatous damage to the optic nerve

Medical Conditions of the Eye

• Cataracts - Clouding of the lens

• Glaucoma - Loss of peripheral or “side” vision

Medical Conditions of the Eye

• Macular Degeneration - Loss of central or

“straight ahead” vision

• Diabetic Retinopathy - Blurring of central

vision to blindness

GlaucomaGlaucoma

Glaucoma management involves lowering IOP by

- Decreasing aqueous production by the ciliary body

- Increasing aqueous outflow through the trabecular meshwork (小梁网 ) and uveal outflow paths（房水排出通道） - Neuroprotection

• pilocarpine: parasympathomimetics

increase aqueous outflow by contraction of the ciliary muscle to increase tone and alignment of the trabecular network

Pilocarpine Increase Aqueous Pilocarpine Increase Aqueous Humor OutflowHumor Outflow

PilocarpinePilocarpine(2) Promoting secretion of exocrine glands, (2) Promoting secretion of exocrine glands,

especially in sweat, salivary and tear glandsespecially in sweat, salivary and tear glands

(3) Gastrointestinal tract: (3) Gastrointestinal tract: increasing tone and motilityincreasing tone and motility

(4) Urinary tract: (4) Urinary tract: contraction of bladder and relax for contraction of bladder and relax for

external sphincter musclesexternal sphincter muscles

(5) Respiratory system: (5) Respiratory system: bronchoconstriction and bronchoconstriction and

secretionsecretion

(5) CNS: (5) CNS: cortical arousal or activationcortical arousal or activation

Muscarinic Agents:Muscarinic Agents: Parasympathetic Effects & Therapeutic Uses Parasympathetic Effects & Therapeutic Uses

Other useOther use

(1) Gastrointestinal disorders, like gastroparesis(1) Gastrointestinal disorders, like gastroparesis

(2) Urinary bladder disorders, urinary retention(2) Urinary bladder disorders, urinary retention

(3) Xerostomia(3) Xerostomia （口腔干燥）（口腔干燥） , ,

(4) Antidote(4) Antidote for atropine poisoning for atropine poisoning

Muscarinic Agents:Muscarinic Agents: Parasympathetic Effects & Therapeutic Uses Parasympathetic Effects & Therapeutic Uses

- - actions at ganglia, NMJ, brain

Actions are complex and frequently unpredictable, because of the variety of neuroeffector sites and becausenicotine both stimulates and desensitizes effectors. Nicotine typically will affect the ：

Periphery: HR, BP, GI tone & motility and alsoCNS: stimulation, tremors, respiration, emetic effects

The addictive power of cigarettes is directly related to their nicotine content.

N receptor agonists:N receptor agonists: NicotineNicotine

1 Cholinomimetics(1 Cholinomimetics(Parasympathomimetics))(1) Direct-acting drugs: Cholinoceptor agonists(1) Direct-acting drugs: Cholinoceptor agonists• M, N receptor agonists:M, N receptor agonists: acetylcholineacetylcholine• M receptor agonists:M receptor agonists: pilocarpinepilocarpine• N receptor agonists:N receptor agonists: nicotinenicotine

(2) Indirect-acting drugs: Cholinesterase inhibitors (2) Indirect-acting drugs: Cholinesterase inhibitors (Anticholinesterases)(Anticholinesterases)

• Reversible: neostigmineReversible: neostigmine• Irreversible: organophosphatesIrreversible: organophosphates


1 Cholinomimetics 1 Cholinomimetics (1) Direct-acting drugs: Cholinoceptor agonists(1) Direct-acting drugs: Cholinoceptor agonists• M, N receptor agonists: M, N receptor agonists: acetylcholineacetylcholine• M receptor agonists: pilocarpineM receptor agonists: pilocarpine• N receptor agonists: nicotineN receptor agonists: nicotine

(2) Indirect-acting drugs: Cholinesterase inhibitors (2) Indirect-acting drugs: Cholinesterase inhibitors (Anticholinesterases)(Anticholinesterases)

• Reversible:Reversible: neostigmineneostigmine• Irreversible:Irreversible: organophosphatesorganophosphates


Cholinergic antagonistsCholinergic antagonists ：： Cholinesterase Cholinesterase reactivatorsreactivators ppralidoxime iodideralidoxime iodide

Cholinomimetics-Cholinomimetics- Indirect Agents: Indirect Agents: AChE InhibitorsAChE Inhibitors

Acetylcholinesterase (AChE) Activity阴离子部位酯解部位

乙酰化 AChE

胆碱

水解

A. Edrophonium 依酚氯铵 (reversible, competitive)

B. Carbamates 氨甲酰类 (slowly reversible)

C. Organophosphates 有机磷类 (irreversible)

Cholinomimetics-Cholinomimetics- Indirect Agents: Indirect Agents: AChE InhibitorsAChE Inhibitors

neostigmineThese agents are These agents are reversiblereversible and are and are

used medically used medically (glaucoma or MG)(glaucoma or MG)

These agents are These agents are irirreversible reversible and and

are used as are used as pesticides or for pesticides or for

glaucomaglaucoma

新斯的明异氟磷

毒扁豆碱

依酚氯铵氨甲酰酚羟基

Acetylcholinesterase Inhibitors: Reversible

Edrophonium 依酚氯铵

Rapidly absorbed; A short duration of action (5-15min);Competitive (reversible)

Used in diagnosis of myasthenia gravis.

Excess drug may provoke a cholinergiccrisis, Atropine is the antidote.

Acetylcholinesterase Inhibitors: Carbamates

Inhibitory Effects are slowly reversible

Representative Drugs neostigmine 新斯的明 (quaternary amine) physiostigmine 毒扁豆碱 (tertiary amine) pyridostigmine 吡斯的明 (quaternary amine)

quaternary amines effective in periphery onlytertiary amines effective in periphery and CNS（ fat-soluble）二甲氨基甲酰化 AChE


neostigmine (quaternary amine)

– Pharmacological effectsPharmacological effects

• AChE(-), Ach AChE(-), Ach ↑↑, directly stimulating N, directly stimulating NMMRR

• stronger effect on skeletal muscles stronger effect on skeletal muscles

• effective on GI tract and urinary bladder effective on GI tract and urinary bladder

• more polar and can not enter CNSmore polar and can not enter CNS

• relatively ineffective on CVS, glands, eyerelatively ineffective on CVS, glands, eye


neostigmine (quaternary amine)

– Clinical usesClinical uses

• Myasthenia gravis:Myasthenia gravis: symptomatic treatment, overdose:

cholinergic crisis

• Paralytic ileus and bladder: Paralytic ileus and bladder: post operative abdominal

distension and urinary retention

• Paroxysmal superventricular tachycardiaParoxysmal superventricular tachycardia （阵发性室上速）（阵发性室上速）

• Antidote for tubocurarine Antidote for tubocurarine （筒箭毒碱）（筒箭毒碱） and related drug and related drug

poisoningpoisoning

neostigmine (quaternary amine) – Adverse effectsAdverse effects• Cholinergic effects: Cholinergic effects: muscarinic and nicotinic effects, muscarinic and nicotinic effects,

treated with atropine (muscarinic)treated with atropine (muscarinic)

• ContraindicationsContraindications ：： mechanical ileus mechanical ileus 机械性肠梗阻机械性肠梗阻 urinary obstruction urinary obstruction 泌尿道梗阻泌尿道梗阻 bronchial asthma bronchial asthma 支气管哮喘支气管哮喘 poisoning of depolarizing skeletal muscle relaxantspoisoning of depolarizing skeletal muscle relaxants

(e.g. succinylcholine(e.g. succinylcholine 琥珀胆碱琥珀胆碱 ) )


Other reversible AChE inhibitors

Pyridostigmine 吡斯的明• Similar as neostigmine, slow but longer durationSimilar as neostigmine, slow but longer duration

Physostigmine 毒扁豆碱• Stronger than neostigmineStronger than neostigmine• No direct action on M and N receptorNo direct action on M and N receptor• Can enter CNS, Can enter CNS, 先兴奋后抑制先兴奋后抑制• Stimulate N receptor of sympathetic nervous nodeStimulate N receptor of sympathetic nervous node

complex effects on cardiovascular systemcomplex effects on cardiovascular system• Stimulate N receptor of skeletal muscle Stimulate N receptor of skeletal muscle 肌束震颤肌束震颤• 主要用于急性青光眼，抗胆碱药中毒，但其本身的毒性较主要用于急性青光眼，抗胆碱药中毒，但其本身的毒性较

大。大。

Other reversible AChE inhibitors

Galanthamine 加兰他敏• Similar as neostigmine, can enter CNS and treat for Similar as neostigmine, can enter CNS and treat for

ADAD

Dihydrogalanthamine 二氢加兰他敏Ambenonium chloride 安贝氯胺Demecarium bromide 地美溴铵Distigmine bomide 溴地斯的明Eseridine 依舍立定Eptastigmine 依斯的明

对硫磷

马拉硫磷

乙膦硫胆碱梭曼

These agents are used as

pesticides or for glaucoma.

Acetylcholinesterase Inhibitors: Irreversible

Bond is hydrolyzed in binding to the enzyme

For ophthalmic useFor ophthalmic use

Acetylcholinesterase Inhibitors: Organophosphates

Effects of Organophosphates are irreversible (covalent bond formation)

Pralidoxime( 碘解磷定 ) can restore AChE activity if administered soon after toxin exposure.

•Conjugating with Conjugating with organophosphate by oxime organophosphate by oxime group; group;

•Conjugating with free Conjugating with free organophasphatesorganophasphates

异氟磷

解磷定

单烷氧基磷酰化 AChE老化

(1) Toxic symptoms(1) Toxic symptoms– Acute intoxicationAcute intoxication• Muscarinic symptomsMuscarinic symptoms eye, exocrine glands, eye, exocrine glands,

respiration, GI tract, urinary tract, CVSrespiration, GI tract, urinary tract, CVS

• Nicotinic symptomsNicotinic symptoms NNNN: : elevation of BP, increase of elevation of BP, increase of

HR;HR; NN22: : tremor of skeletal musclestremor of skeletal muscles

• CNS symptomsCNS symptoms excitation, convulsion(excitation, convulsion( 抽搐抽搐 ); ); depression (advanced phase)depression (advanced phase)

– Chronic intoxicationChronic intoxication• usually occupational poisoningusually occupational poisoning• plasma ChE activity plasma ChE activity ↓,↓,神经衰弱症候群神经衰弱症候群• weakness, restlessness, anxiety, tremor, miosis, ……weakness, restlessness, anxiety, tremor, miosis, ……


(2) Detoxication(2) Detoxication

•Elimination of poison; Supportive therapyElimination of poison; Supportive therapy•AntidotesAntidotes

AtropineAtropine －－ antagonizing muscarinic effects; antagonizing muscarinic effects; early, early, larger dose, and repeated uselarger dose, and repeated use

Cholinesterase reactivatorsCholinesterase reactivators －－ reactivation of reactivation of phosphated AChE; phosphated AChE; moderate-severe patients, early use moderate-severe patients, early use (More effective on tremor), combined with atropine(More effective on tremor), combined with atropine– Pyraloxime chloride (Pyraloxime chloride ( 氯解磷定氯解磷定 )) ：： saver than PAMsaver than PAM– Pralidoxime iodide (PAM) (Pralidoxime iodide (PAM) ( 碘解磷定碘解磷定 ))– Obidoxime chloride(Obidoxime chloride( 双复磷双复磷 ): ): two active oxime two active oxime groupsgroups


glaucoma (e.g. physiostigmine 毒扁豆碱 )

myasthenia gravis (e.g. Edrophonium 依酚氯胺 , neostigmine

新斯的明 , pyridostigmine 吡斯的明 )

reverse neuromuscular blockade from competitive antagonists (neostigmine)

Alzheimer’s disease (tacrine 他克林 & donepezil 多奈派齐 )

chemical warfare agents

insecticides

ACHEI Applications

Pharmacological Actions: Increases ACh concentrations at cholinergic synapses, thereby increasing cholinergic activity.

Summary

Cholinomimetics (Cholinomimetics (Parasympathomimetics))(1) Direct-acting drugs: Cholinoceptor agonists(1) Direct-acting drugs: Cholinoceptor agonists

M, N receptor agonists: M, N receptor agonists: acetylcholineacetylcholine

M receptor agonists: pilocarpineM receptor agonists: pilocarpine

N receptor agonists: nicotineN receptor agonists: nicotine

(2) Indirect-acting drugs: AChE inhibitors(2) Indirect-acting drugs: AChE inhibitors

Reversible: neostigmineReversible: neostigmine

Irreversible: organophosphatesIrreversible: organophosphates

Cholinesterase reactivatorsCholinesterase reactivators ：： PAMPAM

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autonomic pharmacology 张纬萍 浙江大学医学院药理 [email protected] 2013.10.11

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autonomic pharmacology 张纬萍浙江大学医学院药理 [email protected] 2013.10.11