L11 - Cholinergics I

University of Baghdad
College of Medicine
2022-2023
Title: Cholinergics
Grade: 2nd Grade

Module: PP(Principles of Pharmacology)
Speaker: Assistant Proff. Dr.Mohammed Qasim Al Atrakji
Date:9/11/2022
University of Baghdad/ College of Medicine 2022-2023
Dr.Mohammed Qasim
2022-2023
2nd Grade
CHOLINERGIC SYSTEM
Acetylcholine [Ach] an choline ester, is a neurotransmitter of
parasympathetic system.
Nerves which synthesize, stores & release Ach are known as

‘Cholinergic”
SITES OF ACTYLCHOLINE RELEASE:

• GANGLIA- All pre-ganglionic fibers of ANS.[Both in sympathetic &
parasympathetic ganglia.]
• POST GANGLIONIC PARASYMPATHETHIC nerve
endings
• SWEAT GLANDS: Sympathetic postganglionic nerve endings supplying
sweat glands
• SKELETAL MUSCLES- Somatic nerve endings supplying skeletal muscles

• ADRENAL MEDULLA
• CNS- brain & spinal cord
ACETYLCHOLINE (Ach)
• Is major neurotransmitter autonomic & somatic site

• Hemicholinium block choline uptake in axoplasm
• Transport of Ach into synaptic vesicle is blocked
by vesamicol
• Botulinum toxin inhibit Ach release relieve spasm in spastic
disorder, facial wrinkles
Termination of action of Ach
• A specific Acetylcholineesterase present in all

cholinergic sites hydrolyses ester bond choline in μs (very fast)
• Location: All cholinergic sites, RBC, Gray matter
• Nonspecific Butrylcholinesterase (Pseudo) present in plasma

hydrolyses Ach slowly
• Location: Plasma, Liver, Intestine, White matter
Cholinergic receptor
• Muscarine alkaloid mimic the effect of parasympathetic nerve

discharge but not in autonomic ganglia
• Nicotinic alkaloid stimulate autonomic ganglia,

neuromuscular junction but not other autonomic effector cells
Classification
• M-cholinoceptors can be classified into subtypes according to their
molecular structure, signal transduction, and ligand affinity in the M1, M2,
M3 subtypes, etc.
• M1-receptors are present on nerve cells, e.g.,
in ganglia, where they mediate a facilitation of
impulse transmission from preganglionic axon
• terminals to ganglion cells and in Gastric parietal cells
• M2-receptors mediate acetylcholine effects on the

heart. Opening of K+ channels leads to slowing of diastolic
depolarization in sinoatrial pacemaker cells and a decrease in heart rate.
• M3-receptors are found in the glandular epithelia (which respond with activation of
phospholipase C and increases secretory activity) and in smooth muscle.
• In smooth vessels, the relaxant action of ACh on muscle tone is indirect, because it involves
stimulation of M3-cholinoceptors on endothelial cells that respond by liberating NO.
• In the CNS, where all subtypes are present, cholinoceptors serve diverse functions, including
regulation of cortical excitability, memory, learning, pain processing, and brain stem motor
control.
Characteristic of Nicotinic receptors
• NM-cholinoceptors
• Location: neuromuscular junction
• Function: depolarization of muscle end plate and contraction of
skeletal muscle
• NN-cholinoceptors
• Location: autonomic ganglia
• Function: depolarization postganglonic membrane (in adrenal medula
–catecholamine release)
Cholinergic Drugs
• Choline esters
• Acetylcholine
• Bethanechol
• Carbachol
• Methacholine
• Alkaloid
•Muscarine
•Arecoline
•Pilocarpine
Acetylcholine (Prototype)
• Orally destroyed, given iv destroyed by pseudocholinesterase in

plasma & at the site of
action by cholinesterase
• Nonspecific in action
• Not used therapeutically

Physiology of Ach & action in vitro University of Baghdad/ College of Medicine 2022-2023
preparation
• Eye-(M3)
• Sphincter muscle of iris-contraction(miosis)
• Ciliary muscle-contraction for near vision
• Blood vessels (M3)

• Vasodilatation is primarily mediated through
endothelium derived relaxing factor(EDRF) which
is nitric oxide
• In vivo parasympathetic stimulation effects appears as fall in BP and

flushing esp. in blush area of face which has cholinergic innervation
• Bronchial smooth muscle constrict bronchoconstriction

• Detrusor muscle contract while bladder trigone & sphincter relax-

Voiding of urine
• Glands
• • Glands- sweating, salivation, lacrimation
• Skeletal muscle(NM)
• Ach to muscle end plate causes contraction of
fibre
• High dose can cause twitching & fasciculations
Ach substitute
• Effective orally, more selective in their action

• Methacholine –
• Less susceptible to acetylcholinesterase, totally
resistant to pseudocholinesterase
• Carbachol, Bethanechol resistant to hydrolysis of
both true and pseudocholinesterase
• Bethanechol(M3)have negligible effects on CVS (M2),no nicotinic
action
CARBACHOL
• Ester of carbamic acid
• Has both muscarinic and nicotinic actions
• Muscarinic actions are prominent on eye, GIT & urinary bladder
• DOA more than 30 min
• Therapeutic uses:
Glaucoma
METHACHOLINE
• Has methyl group in its structure
• Has both muscarinic and nicotinic actions (very mild
nicotinic actions )
• Muscarinic actions are prominent on CVS
• Longer DOA as compared to ACh
• Therapeutic uses: given SC for the relief of paroxysmal
atrial tachycardia
BETHANECHOL University of Baghdad/ College of Medicine 2022-2023
• Structure related to Ach, acetate is replaced by carbamate &

choline is methylated
• Has no nicotinic actions
• Muscarinic actions are prominent on eye, GIT & urinary
bladder
• Prolonged DOA
• Therapeutic uses:
• Post operative Gastric distension
• Paralytic ileus
• Bladder atonia
Adverse effects
• • Extension of pharmacological action

• • Flushing, salivation, sweating, bradycardia,
bronchospasm, hypotension
• Uses
• Post-operative paralytic ileus, Urinary retention, abdominal
distension
• Bethanechol is preferred drug due to specific
action & wider margin of safety

L11 - Cholinergics I

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University of Baghdad

Grade: 2nd Grade

Nerves which synthesize, stores & release Ach are known as

SITES OF ACTYLCHOLINE RELEASE:

• SKELETAL MUSCLES- Somatic nerve endings supplying skeletal muscles

• Is major neurotransmitter autonomic & somatic site

Termination of action of Ach

• A specific Acetylcholineesterase present in all

• Nonspecific Butrylcholinesterase (Pseudo) present in plasma

• Muscarine alkaloid mimic the effect of parasympathetic nerve

• Nicotinic alkaloid stimulate autonomic ganglia,

• M2-receptors mediate acetylcholine effects on the

Characteristic of Nicotinic receptors

• Orally destroyed, given iv destroyed by pseudocholinesterase in

• Not used therapeutically

• Blood vessels (M3)

• In vivo parasympathetic stimulation effects appears as fall in BP and

• Bronchial smooth muscle constrict bronchoconstriction

• Detrusor muscle contract while bladder trigone & sphincter relax-

• Effective orally, more selective in their action

• Structure related to Ach, acetate is replaced by carbamate &

• • Extension of pharmacological action

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