ANS Pharmacology (Intro) - Dr. Agung

INTRODUCTION TO
AUTONOMIC NERVOUS SYSTEM (ANS)

PHARMACOLOGY
A. N. Mahendra
Department of Pharmacology & Therapy

Faculty of Medicine, Udayana University
 Full Name : Agung Nova Mahendra
 Research Areas: antioxidant pharmacology, experimental CV
neuropsychopharmacology, cardiovascular pharmacology
Level of Education Alma mater Degree / Awards

Senior High School SMAN 1 Singaraja 1st Winner, GLB VI 2002
Silver Medal, OSN 2003
Undergraduate (S1) Fakultas Kedokteran dr.; S.Ked. / Cum Laude
UNUD (2010)
Postgraduate (S2) in Fakultas Kedokteran M.Sc. / Certificate of

Pharmacology UGM Summa Cum laude
(2015)
Postmaster Research Yakko Kaiseki Gaku, Certificate of Excellence
Fellowship in Medicinal Yakko Gakubu, in Neuropharmacology
Pharmacology Okayama Daigaku, (2015)
Okayama, Japan
Training in Molecular Institute of Molecular Certificate of Training
Biology & Animal Science Medicine – NCKU, (2017)
Tainan, R.O.C. Taiwan
Anatomy of the lecture
• Introduction
• Anatomic aspects of the ANS
• Neurotransmitter aspects of the ANS
• Receptor characteristics
• Effects of activating autonomic nerves
• Nonadrenergic, noncholinergic (NANC) transmission
• Sites of autonomic drug action
• Functional integration of the ANS
The importance of understanding
ANS pharmacology
ANS is classically known to control nearly all bodily
functions (cardiac muscles, smooth muscles, glands)
ANS involvement is implicated in many disorders/diseases
Many drugs may affect ANS

(therapeutic, side, & toxic effect)
Serves as a basis for higher medical education

Recent advances on ANS study
Evidence is increasing that ANS is also

involved in:
• Psychiatric disorders
• Motor learning processes
• Hepatic circadian activity
• Tumorigenesis & tumor progession
• Pancreatic β-cells neogenesis
• etc.
List of Terms
• Sympathomimetics/Adrenomimetics
• Sympatholytics /Antiadrenergics or Adrenoceptor
antagonists
• Cholinomimetics/Cholinergics
• Cholinesterase regenerators
• Parasympatholytics/Anticholinergics or Cholinoceptor
antagonists
• Dopaminergics
(Mathias, 2003)
Creative thinking….
 SANS: “Flight or Fight Response”
 PANS: “Rest & Digest” (“See-Spit-Pee-Shit”)

Neurotransmitter aspects of the ANS
NOREPINEPHRINE:
primary transmitter of
SANS  adrenoceptor &
noradrenergic
neuron/synapse
ACETYLCHOLINE:
COTRANSMITTERS:
primary transmitter of
ATP, VIP, NPY,
PANS  cholinoceptor
substance P,
& cholinergic
somatostatin, etc.
neuron/synapse
Neurotransmitters involved in the ANS pathways…
(Mathias, 2003)
Many drugs exert their effects by working at
different steps of autonomic transmission:
Synthesis
Uptake &
Metabolism Storage
Receptor
Release
Interaction
Presynaptic neuron CHOLINERGIC NEURON
1.
Acetyl-CoA + Choline Choline Drugs affecting
cholinergic activity:
1. Hemicholinium
2.
ACh-containing 2. Vesamicol
vesicle 3. Botox
Ca2+
+
3. Vesicle docking &

fusion;
ACh release
ACh
AChE
Cholinoceptor
Acetate & Choline
Postsynaptic neuron
Presynaptic neuron NORADRENERGIC NEURON
Tyrosine Tyrosine
Mt TH 1.
(with DOPA
MAO) Drugs affecting
AT II R
DA* noradrenergic
2. M1 R activity:
NE-containing
α2 R
1. Metyrosine
vesicle
2. Reserpine
Ca2+ 3. Guanethidine,
NE ++
uptake Vesicle docking &
4. Cocaine, Tricyclic
3.
4. fusion; antidepressants
NE *(& DA) (TCAs)
NE release
Adrenoceptor
Diffusion & Metabolism

Postsynaptic neuron
Receptor characteristics
Cholinoceptors:
Muscarinic & Nicotinic
Major ANS receptor

systems
Adrenoceptors:
Alpha & Beta
Dopamine receptors
Cholinoceptors
Type Mechanism Location

M1 Gq  increases IP3 & DAG Nerve endings
M2 Gi  decreases cAMP, activates K+ Heart, some nerve

channels endings
M3 Gq Effector cells: SM,

glands, endothelium
NN Ion channel  depolarization ANS ganglia
NM Ion channel  depolarization NMJ

Adrenoceptors & Dopaminergic Receptors
Type Mechanism Function Location
α1 Gq Increases Ca2+  Effector tissues: SM,

contraction & secretion glands
α2 Gi Reduces transmitter release Nerve endings &

 contraction some SM
β1 Gs Inotropic & chronotropic Cardiac muscle &

(+); increases renin release JGA
Β2 Gs Inotropic & chronotropic Heart, liver, & SM

(+); increases
glycogenolysis; relax SM
β3 Gs Increases lipolysis Adipocytes
D1 Gs Relax renal vascular SM SM

Effects of autonomic nerves activation:
the eye as model organ
E.g.: Pupil is both innervated

Each ANS division has
by SANS & PANS fibers (with
specific effects on organ
α-adrenoceptors & M
systems
receptors, respectively)
Sympathetic innervation of the pupil: Example of autonomic
nerves activation
SANS
Pupil
α1
receptor
Radial muscle of
the iris (m.
dilator pupillae)
Mydriasis
Parasympathetic innervation of the pupil: Example of autonomic
nerves activation
PANS
Pupil
M receptor
Circular muscle of the

iris (m. constrictor
pupillae)
Miosis
Nonadrenergic, noncholinergic
(NANC) transmission
Some nerve fibers in autonomic effectors tissues

do not exhibit the histochemical characteristics
of either cholinergic or adrenergic fibers
E.g.: purine-responsive fibers in bronchi, GIT, UT

& peptidergic motor fibers (NPY, VIP, etc.)
Sites of autonomic drug action
The sites include CNS
centers, ganglia,
There are many sites of drug postganglionic nerve
action (e.c. multistep nature terminals, effector cell
of ANS transmission) receptors, & steps of
autonomic transmission
Selectivity is mostly
achieved by drugs acting @
receptors with very selective
actions
Functional integration of the ANS
• Mainly based on negative feedback
• Two levels of integration
Modulatory pre- &

Local integration postsynaptic receptors
Autonomic
integration
Systemic Systemic homeostatic
integration reflexes
Local integration
Autoreceptor vs. Heteroreceptor 

presynaptic modulation
Postsynaptic modulatory receptors (M &

at least 1 type of peptidergic receptors)
in ganglionic synapses where nicotinic
transmission is primary  EPSP or IPSP
Presynaptic neuron
NORADRENERGIC
Tyrosine Tyrosine NEURON
Mt
(with DOPA
MAO) AT II R
DA* HETERORECEPTORS
M1 R
NE-containing
α2 R AUTORECEPTORS
vesicle
Ca2+
NE ++
uptake Vesicle docking &
fusion;
NE *(& DA)
NE release
Adrenoceptor
Diffusion & Metabolism

Postsynaptic neuron
Systemic integration: symphony of
autonomic nervous & endocrine system
Increased blood
pressure to normal
Increased level
Decreased HR & CO
PANS
Vasomotor (vagal)
center tone &
Baroreceptors increased
increase firing SANS tone
Reduced blood
pressure
Increases renin release  RAAS
AT II increases PVR; activation
aldosterone causes salt &
water retention
Summary
The ANS (PANS & SANS) involves various types of
neurotransmitter to regulate bodily functions, with ACh & NE
as primary neurotransmitters
Cholinergic & Adrenergic systems mainly work to

counterbalance one another
Autonomic drugs exert their effects on various components of

autonomic transmission
Both local & systemic integration have important contribution

on the functional integrity of ANS. Negative feedback is
extensively used by ANS to regulate its functions
References
• Trevor AJ, Katzung BG, Masters SB. Katzung & Trevor’s Pharmacology
Examination & Board Review 11th edition. The McGraw-Hill Companies. 2009:77-
94.
• Mathias CJ. Autonomic Diseases: Clinical Features and Laboratory Evaluation. J
Neurol Neurosurg Psychiatry. 2003(74): 31-41.
• Katzung BG, Masters SB, Trevor AJ. Basic & Clinical Pharmacology 13th edition.
The McGraw-Hill Companies. 2015:87-168.
TERIMAKASIH
MATUR SUKSMA
MATUR NUWUN
THANK YOU
ARIGATOU
GOZAIMASU
XIÈ XIE

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INTRODUCTION TO

AUTONOMIC NERVOUS SYSTEM (ANS)

Department of Pharmacology & Therapy

Level of Education Alma mater Degree / Awards

Postgraduate (S2) in Fakultas Kedokteran M.Sc. / Certificate of

ANS involvement is implicated in many disorders/diseases

Many drugs may affect ANS

Serves as a basis for higher medical education

Evidence is increasing that ANS is also

 SANS: “Flight or Fight Response”

 PANS: “Rest & Digest” (“See-Spit-Pee-Shit”)

3. Vesicle docking &

Diffusion & Metabolism

Major ANS receptor

Type Mechanism Location

M2 Gi  decreases cAMP, activates K+ Heart, some nerve

M3 Gq Effector cells: SM,

NN Ion channel  depolarization ANS ganglia

NM Ion channel  depolarization NMJ

α1 Gq Increases Ca2+  Effector tissues: SM,

α2 Gi Reduces transmitter release Nerve endings &

β1 Gs Inotropic & chronotropic Cardiac muscle &

Β2 Gs Inotropic & chronotropic Heart, liver, & SM

β3 Gs Increases lipolysis Adipocytes

D1 Gs Relax renal vascular SM SM

E.g.: Pupil is both innervated

Circular muscle of the

Some nerve fibers in autonomic effectors tissues

E.g.: purine-responsive fibers in bronchi, GIT, UT

Modulatory pre- &

Autoreceptor vs. Heteroreceptor 

Postsynaptic modulatory receptors (M &

Diffusion & Metabolism

Cholinergic & Adrenergic systems mainly work to

Autonomic drugs exert their effects on various components of

Both local & systemic integration have important contribution

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