Section Ⅱ

 Autonomic Drugs

Autonomic nervous
Chapter 6 Introduction to
system (ANS) is largely
independent on
consciousness.
vegatable
Autonomic Pharmacology
Cao Yongxiao 曹永孝

Department of Pharmacology

029-8265 5140; yxy@xjtu.edu.cn

http://pharmacology.xjtu.edu.cn

1
Anatomy of the Peripheral Nervous System
The peripheral
The nervous systemnervous
is divided
system intoisthe
(PNS) further
central nervous
divided into the
system (CNS)
afferent and
NS bringing
the peripheral
information from the
nervous system
periphery to the CNS
(PNS).
and

efferent NS carrying
signals away from the
CNS to the peripheral
tissues.
 The efferent
NS is further
divided into
the
autonomic
nervous
system
(ANS) and
somatic
motor
nervous
system
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 The somatic motor nervous system
innervates skeletal muscles which receive
only one efferent neuron.

precise
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The ANS is further
divided into
sympathetic and
parasympathetic
nervous systems

The autonomic nervous

system innervates viscera
such as heart, smooth
muscle, and glands etc.
Target tissues receive two
types of efferent neurons,
sympathetic and
parasympathetic nerves.
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There are ganglia between the CNS and the
effectors innervated by autonomic nerve system.

Preganglionic fiber, ganglion, postganglionic fiber

Neurotransmitter Chemistry of ANS
The classification of efferent nerves is based on the
transmitter--acetylcholine (ACh)or norepinephrine (NE)
released from their terminals.
1) Cholinergic
fibers:

It is fibers
releasing ACh
2) noradrenergic
fibers:

3) Other fibers:
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 1) Cholinergic fibers include:
Cholinergic
• somatic motor fibers,
2) noradrenergic fibers: fibers:
• Most postganglionic
preganglionic sympathetic
autonomic fibers, fibers release
• a fewIt sympathetic
is fibers
norepinephrine.
• parasympatheticThey are noradrenergic fibers.
fibers, releasing
ACh
3) Other fibers: release adrenaline, dopamine and peptides.
postganglionic
fibers (controlling
sweat gland and
blood vessel in
skeletal muscle)
• nervous fibers
controlling adrenal
medulla.
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Chemical Transmission in Autonomic NS
Transmitter:
Synapse:
ItIt isisthe
thejunction
chemical
of nerve
agent released
terminal from
with the next
neuron
nerve orterminal
effector that
cell,
consisting of presynaptic
transmits information
membrane, postsynaptic
across synapse and
membrane and synaptic
to effectors.
space.
pre post
Synapse
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This triggers the fusion of The transmitters diffuse
Action
potential （ AP ） pa
vesicles containing across the cleft and bind
ssing down an axon
neurotransmitters and cell to receptors on the
to the axon terminal postsynaptic membrane
membrane, and causes the
changes membrane to induce a response in
release of neurochemical
polarization the postsynaptic neuron.
(neurotransmitter) into the
synaptic cleft.

resulting in
Ca2+ entry into
the cell.
Chemical Transmission in synapse
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 Cholinergic Transmission Choline is
transported into
ACh is the presynaptic
synthesized nerve terminal
from acetyl
by a carrier (A)
coenzyme A
(Ac-CoA) and Once
choline synthesized, ACh
through the is transported
catalytic into and
action of packaged in the
choline acetyl vesicles.
transferase
(ChAT).

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 Cholinergic Transmission When an AP reaches
the terminal and
triggers influx of Ca2+
which facilitates the
After fusion of the vesicular
release, ACh membrane with the
terminal membrane
bind to and and results in the
activate pre- release of ACh into
and synaptic space.

postsynaptic Then, ACh is

acetylcholine hydrolyzed rapidly
receptors by acetylcholin-
(cholinocept esterase (AChE),
or), showing terminating the
action of the
the action of
transmitter.
transmitter.
 Cholinergic
Transmission

 Fig. Action potential-

induced release of the
neurotransmitter
acetylcholine (ACh)
and its metabolism at
the neuromuscular
junction.
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Adrenergic Transmission
Tyrosine is
transported actively
Norepinephrine,NE
. into the
Dopa is
noradrenergic ending
decarboxylated
and to
is converted to
dopamine
dopa by
by tyrosine
dopa
hydroxylase
decarboxylase.
Dopamine is
transported into the
vesicles and then
converted to NE by
dopamine-beta-
hydroxylase. In the
adrenal medulla, NE is further
converted to epinephrine.
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 An action potential
causes an influx of
.
Ca2+ into the nerve
terminal, fusion of the
vesicle with the
plasma membrane
and exocytosis of
NE.
The transmitter
then activates
receptors in the
postsynaptic
membrane.

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 NE in the synaptic
space is actively
. reuptaken into the
nerve and the
storage vesicles
(uptake l). It is the
most important
NE penetrates
mechanism for into
smooth cells of
termination (uptake
the
2) and diffuses away
action.
from the receptor
site, is inactivated
by COMT (enzyme) to
normetanephrine
(NMN).
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2 ． NA 的合成、释放与灭活：主要在神经末梢合成
Another portion of the NE
合成：酪氨酸从血进人神经元 多巴 多巴胺
reuptaken NA
into the nerve is
酪氨酸 多巴 多巴胺

deaminated by MAO enzyme

羟化酶
. 脱羧酶 β- 羟化酶

贮存：合成的 NA 与 ATP 和嗜铬颗粒蛋白结合贮存于囊泡中。

释放：
神经冲动到达前膜
，NE can also
NA 胞裂外排进入突
activate
触间 隙，与受体结合产
presynaptic (α2)
生效 应

receptors, to
终止：
突触间隙中的 NA
inhibit further
大部分被再摄入神
经末梢囊泡中贮存
release
［摄取 1of
］ NE.

少量在非神经组织
，
被 COMT 和 MAO
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Autonomic Receptors G protein-coupled receptor

Receptor: The
膜受体的最大家系 receptive
substances (protein) of a
cell that specifically bind,
interact多巴胺
肾上腺素 with ligands, and Receptors of
5-HT M- 乙酰
transmit information. autonomic nerve
胆碱多肽类 前列
腺素 阿片类 嘌
system include
呤类 cholinoceptors,
adrenoceptors
第二信使
and dopamine
蛋白激酶 A 、 C 、 receptors
G
钙调素依赖蛋白
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 1 Cholinoceptors :
The receptors combined with ACh are classified
as muscarinic and nicotinic receptors.

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 2 Adrenoceptors:
The receptors combined with NE and adrenaline
include two groups

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Receptor’s Function

Most of organs are

innervated by both of
the sympathetic and
parasympathetic
nervous system.

The two systems

generally have
opposing effects.
But, they are uniform
in vivo
1) Sympathetic
activity

Both NE and Ad bind

to α-adrenoceptors,
β-adrenoceptors and
induce respective
effects.
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 (1) Vascular constriction of skin,
1. Effects of α
splanchnic, and mucosa
increases blood pressure.
(2) Radial muscle of iris
contracts to dilate pupil
(mydriasis).
(3) Contracting sphincters of
gastrointestinal tract and
urinary bladder.
(4) Secretion of sweat glands in
palms of hands.
(5) Glycogenolysis of liver
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increase blood sugar.
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2) β1 effects
2．(1)β Cardiac
型肾上腺素受体 (β 受体
stimulation )
enhancing the force, rate and
主要分布在交感神经节后纤维所支配的效应器，再分为 4 种亚
conduction
型 of the heart.
(2) Renin secretion.
β 受体：主要位于心脏、肾小球旁系细胞
1
选择性激动药为地诺帕明，阻断药为美托洛尔；
效应：心脏兴奋。
3) β 2 effects
(1)β2 受体
Dilatation of artery in skeletal muscles and the heart.
：主要位于支气管平滑肌、骨骼肌血管和冠状血管、肝脏。
其选择性激动药为特布他林，阻断药为布他沙明
； (2) Relaxation of bronchus, gastrointestinal and
genitourinary smooth效应：支气管平滑肌松弛，血管舒张，分解脂糖
muscle.
。
(3) Glycogenolysis 突触前膜and gluconeogenesis of liver.
β2 效应：正反馈调节去甲肾上腺素释
放。
 
4) β3β3effects
受体：主要分布在脂肪细胞，多数 β 受体阻断药不能阻断 β3 受体
lipolysis of fat cells. metabolic
β 受体：亦主要分布在心脏，尚无选择性激动药和阻断药。
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 2. M effects:
1) Inhibiting heart (M2) to
decrease heart rate,
conduction and contractility.
2) Vasodilation of artery
3) Contraction of
bronchial, gastrointestinal and
genitourinary smooth
muscles, but relaxation of
sphincters
4) Increasing secretion
(M3) of salivary, respiratory
and gastrointestinal tract
glands
5) Eye (M3): miosis. near
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 3. Dopamine receptors 多巴胺受体

Dl 受体：位于肾、肠系膜、心、脑等血管平滑肌及心肌的多巴胺受体

D2 受体：位于交感神经节及突触前膜的多巴胺受体。

There are 5 subtypes of dopamine receptors.

Dl receptor is the most important. It locates in

vascular smooth muscle cells, brain etc.
It can dilate blood vessel, decrease
peripheral vascular resistance and increase
urinary volume.
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 Drug Classification of ANS
1. Effects on Receptors
1) Agonist (high intrinsic activity)
cholinoceptor-activating drugs
M and N receptor agonist: ACh
M receptor agonist: Pilocarpine
N receptor agonist: Nicotine
adrenoceptor-activating drugs
αand β receptor agonist: Adrenaline
α agonist. NE
β agonist: Isoprenaline
2) Antagonist (no intrinsic activity)
cholinoceptor-blocking drugs
M receptor blocker: atropine
N1 receptor blocker: hexamethonium
N2 receptor blocker: tubocurarine
adrenoceptor antagonist drugs
αreceptor blocker: phentolamine
α1 receptor blocker: prazosin
β receptor blocker: propranolol
αandβreceptor blocker: labetolol
2. Influencing transmitters
1) Influencing metabolism of ACh
Anticholinesterases: Neostigmine (cholinomimetics)
Cholinesterase reactivators: PAM (anticholinergics)
2) Influencing transportation of NE
Sympatholytics: Reserpine: inhibit uptake of NE
from synapse to vesicles and
prevent storage depletion of vesicles
release of NE BP
Adrenergics: Ephedrine releasing NE