Introduction Of ANS

1. 1
Section Ⅱ
Autonomic Drugs
Introduction to
Autonomic Pharmacology
Dr. Maria Qammar
Assistant Professor Pharmacology

2. Anatomy of the Peripheral Nervous System
The nervous system
is divided into the
central nervous
system (CNS) and
the peripheral
nervous system
(PNS).
The peripheral nervous
system (PNS) is further
divided into the
afferent NS bringing
information from the
periphery to the CNS
and
efferent NS carrying
signals away from the
CNS to the peripheral
tissues.

3. The efferent
NS is further
divided into
the
autonomic
nervous
system (ANS)
and somatic
motor
nervous
system
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4.  The somatic motor nervous system
innervates skeletal muscles which receive
only one efferent neuron.
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precise

5. 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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6. There are ganglia between the CNS and the
effectors innervated by autonomic nerve system.
Preganglionic fiber, ganglion, postganglionic fiber

7. 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:

8. 1) Cholinergic fibers include:
• somatic motor fibers,
• preganglionic autonomic fibers,
• parasympathetic fibers,
Cholinergic
fibers:
It is fibers
releasing
ACh
• a few sympathetic
postganglionic
fibers (controlling
sweat gland and
blood vessel in
skeletal muscle)
•
2) noradrenergic fibers:
Most postganglionic sympathetic fibers release
norepinephrine. They are noradrenergic fibers.

9. Synapse:
It is the junction of nerve
terminal with the next
neuron or effector cell,
consisting of presynaptic
membrane, postsynaptic
membrane and synaptic
space.
pre post
Chemical Transmission in Autonomic NS
Transmitter:
It is the chemical
agent released from
nerve terminal that
transmits information
across synapse and
to effectors.
Synapse
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10. Action potential
（AP）passing
down an axon to the
axon terminal
changes membrane
polarization
resulting in
Ca2+ entry into
the cell.
This triggers the fusion of
vesicles containing
neurotransmitters and cell
membrane, and causes the
release of neurochemical
(neurotransmitter) into the
synaptic cleft.
The transmitters diffuse
across the cleft and bind
to receptors on the
postsynaptic membrane
to induce a response in
the postsynaptic neuron.
Chemical Transmission in synapse
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11. Cholinergic Transmission Choline is
transported into
the presynaptic
nerve terminal
by a carrier (A)
Once
synthesized, ACh
is transported
into and
packaged in the
vesicles.
ACh is
synthesized
from acetyl
coenzyme A
(Ac-CoA) and
choline
through the
catalytic
action of
choline acetyl
transferase
(ChAT).
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12. Cholinergic Transmission
After release,
ACh bind to
and activate
pre- and
postsynaptic
acetylcholine
receptors
(cholinocept
or), showing
the action of
transmitter.
Then, ACh is
hydrolyzed rapidly
by acetylcholin-
esterase (AChE),
terminating the
action of the
transmitter.
When an AP reaches
the terminal and
triggers influx of Ca2+
which facilitates the
fusion of the vesicular
membrane with the
terminal membrane
and results in the
release of ACh into
synaptic space.

13. Cholinergic
Transmission
 Fig. Action potential-
induced release of the
neurotransmitter
acetylcholine (ACh)
and its metabolism at
the neuromuscular
junction.
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14. 西安交大医学院药理学系 曹永孝 yxy@xjtu.edu.cn; 029-82655140
.
Tyrosine is
transported actively
into the
noradrenergic ending
and is converted to
dopa by tyrosine
hydroxylase
Dopa is
decarboxylated to
dopamine by
dopa
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.
Adrenergic Transmission
Norepinephrine,NE

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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.

16. 西安交大医学院药理学系 曹永孝 yxy@xjtu.edu.cn; 029-82655140
.
NE in the synaptic
space is actively
reuptaken into the
nerve and the
storage vesicles
(uptake l). It is the
most important
mechanism for
termination of the
action.
NE penetrates into
smooth cells (uptake 2)
and diffuses away
from the receptor
site, is inactivated
by COMT (enzyme) to
normetanephrine
(MAO).

17. 膜受体的最大家系
肾上腺素 多巴胺
5-HT M-乙酰胆碱
多肽类 前列腺素
阿片类 嘌呤类
第二信使
蛋白激酶A、 C、 G
钙调素依赖蛋白
DNA依赖蛋白激酶
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Autonomic Receptors G protein-coupled receptor
Receptor: The receptive
substances (protein) of a
cell that specifically bind,
interact with ligands, and
transmit information.
Receptors of
autonomic nerve
system include
cholinoceptors,
adrenoceptors
and dopamine
receptors

18. 1 Cholinoceptors :
The receptors combined with ACh are classified
as muscarinic and nicotinic receptors.
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19. 2 Adrenoceptors:
The receptors combined with NE and adrenaline
include two groups
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20. 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

21. 1) Sympathetic
activity
Both NE and Ad bind
to α-adrenoceptors,
β-adrenoceptors and
induce respective
effects.
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22. (1) Vascular constriction of skin,
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
increase blood sugar.
1. Effects of α
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23. 2．β型肾上腺素受体 (β受体)
主要分布在交感神经节后纤维所支配的效应器，再分为4种亚型
β1受体：主要位于心脏、肾小球旁系细胞
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。
β2受体：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；
效应：支气管平滑肌松弛，血管舒张，分解脂糖。
突触前膜β2效应：正反馈调节去甲肾上腺素释放。
β3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
β4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) β1 effects
(1) Cardiac stimulation enhancing the force, rate and
conduction of the heart.
(2) Renin secretion.
3) β 2 effects
(1) Dilatation of artery in skeletal muscles and the heart.
(2) Relaxation of bronchus, gastrointestinal and
genitourinary smooth muscle.
(3) Glycogenolysis and gluconeogenesis of liver.
4) β3 effects
lipolysis of fat cells. metabolic

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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
vision.

25. 3. Dopamine receptors 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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27. 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

28. 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

29. 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