Nervous System

Central Nervous System Somatic Nervous System

Peripheral Nervous System

Autonomic Nervous System

Parasympathetic Nervous System

Sympathetic Nervous System

CNS : . : ... = Autonomic

2
ganglion preganglionic postganglionic

organ

C N S
muscle
NMJ motor end plate

2-

Sympathetic

Parasympathetic

Parasympathetic
: preganglionic fiber postganglionic fiber 1:1 = homeostasis (housekeeping) * * * *

Sympathetic
: preganglionic fiber postganglionic fiber 1:20 = ganglia chains adrenal medulla * * * *

- fight or flight

:
Acetylcholine (ACh) NorEpinephrine = NorAdrenaline (NE = NA)

The Peripheral Nervous System

: ACh ( NAChR)
ganglion

ACh - NE
C (ACh) N S
organ

* *

:
, , : : , : * * *

1. 2. 3. = 4. 5.

ACh
Choline + Acetyl-CoA
CAT

Acetylcholine CHOLINE
* : * *

Na+

Hemicholinium :

ACh
Choline + Acetyl-CoA
CAT

Acetylcholine

Acetyl-CoA
: *

CAT - Choline Acetyl Transferase

: * *

* H+ ions ) ACh vesamicol, AH5183 ACh 300,000 * ( * * *

1,000-50,000 : - motor endplate

(Exocytosis)
[Ca+2]
synaptotagmin synaptobrevin

"

- botulinum toxin
(BOTOX)

Acetylcholine AChE Choline + Acetate Acetylcholine Esterase

ACh = AChE * * *

carbamate derivatives : organophosphates

2
nicotine muscarine .1 .2

Nicotinic receptors
5* ionotropic * Na+ : NN NM > : * * *

Muscarinic receptors
:G A.C n Gi o PLC n Gq M1 M5 ( (GPCR) : 5* *

Cloning ) pharmacological tools

PLC

Gq

CNS heart

M1 M2 M3 M4 M5

A.C. Gi Open K+ channel Block Ca2+ channel PLC Gq

A.C. Gi Open K+ channel Block Ca2+ channel PLC Gq

Smooth muscle/ Glands CNS

CNS/periphery

RECEPTOR
PRE SYNAPTIC
AUTO RECEPTOR HETERO RECEPTOR

POST SYNAPTIC

Cholinomimetics
Direct Indirect
AChE amplifiers

Esters

Alkaloids

Structure Activity Relationship (S.A.R)

Structure Activity Relationship

O C H3C O CH2 CH2

+N

CH3 CH3 CH3 + :

Acetylcholine

Structure Activity Relationship

M N AChE +++ +++ +++

Acetylcholine
O C O CH2 CH2
+N

CH3 CH3 CH3

H3C

Methacholine
M N AChE +++ +

O H3C C O CH CH3 CH2

+N

CH3 CH3 CH3

Structure Activity Relationship

Carbachol
M N AChE +++ +++ -

O C O CH2 CH2
+N

CH3 CH3 CH3

H2N

M N AChE +++ -

Bethanechol
O CH3 O CH CH3 CH2
+N

H2N

CH3 CH3

Structure Activity Relationship

AChE
AChE +++ + M +++ +++ +++ +++

, N
+++ +++ Acetylcholine Methacholine Carbachol Bethanechol

Structure Activity Relationship

- CH2 N CH3 - (C2H5)

* *

qq
O

CH3 CH3

H3C C O CH2 CH2 N+ CH3

Structure Activity Relationship

: O CH3 CH3

H3C C O CH2 CH2 N+ CH3

Structure Activity Relationship

,
H3C CH2 CH2

N CH3

Pilocarpine
O O N N

Nicotine
N CH3

Structure Activity Relationship

Quaternary Alkaloid

HO CH3 H3C
+N

Muscarine
CH3 CH3

CH2

:
) -

( M2 :
(bradycardia)

* chronotropic * *

inotropic SA-node

:ACh

-1

A.C.

M2-AChR * vagal stimulation * -2 M-AChR *

(heteroreceptors )

M3 M3AChR NO

Baroreceptors
:
(set point)

(accelerans)

Baroreceptors-

Vasomotor Center (vagus) -

Baroreceptors
:
(set point)

(accelerans)

Baroreceptors-

Vasomotor Center (vagus) -

Sir Henry Dale (1875-1968) ACh ( )

I.V. injection: ACh 2 Qg ACh 50 Qg

ATROPINE 1mg

ACh 2 Qg 50 Qg 5 mg

B.P.

BRADYCARDIA

PULSE RATE
Reflex Tachycardia

TACHYCARDIA

Gastro-Intestinal
peristalsis

-:

Exocrine glands:

Miosis -

AChE

* * *

.I
( -M) Bethanechol
* * paralytic ileus detrusor S.C P.O. :

) Pilocarpine
* 24 -

Glaucoma -

.II
Ipratropium Donezepil, Galantamine -

BOTULINUM TOXIN - BOTOX

FDA "

(Torticollis) Blepharospasm Strabismus (

FDA "