The document provides an overview of the nervous system and cholinergic transmission. It describes the central nervous system, peripheral nervous system, autonomic nervous system and its sympathetic and parasympathetic divisions. It discusses the cholinergic receptors, muscarinic and nicotinic, their locations, functions and the effects of cholinergic agonists. It also summarizes the uses, mechanisms and side effects of cholinomimetic drugs like acetylcholine, anti-cholinesterases and cholinergic alkaloids in various organs.

2. Nervous System: Overview
Nervous System (NS)
Central Nervous
System(CNS)
Cerebrum, Cerebellum,
Brainstem, Spinal Cord
Peripheral Nervous System
(PNS)
Somatic Nervous
System
Autonomic Nervous
System (ANS)
Sympathetic Nervous
System
Parasympathetic Nervous
System

3. Autonomic Nervous System:
Organization

4. Sympathetic vs Parasympathetic NS
NE
ACh
ACh

5. Cholinoceptors
•Muscarinic (GPCRs)
•SelectiveAgonist: Muscarine
•Antagonist:Atropine
•Five Subtypes: M1-M5
•M1, M3, M5: excitatory (Gq)
•Nicotinic (ligand gated ion
channel)
•SelectiveAgonist: Nicotine
•Antagonist: d-tubocurarine
•Two subtypes: NN & NM
•Usually excitatory

6. Muscarinic Cholinoceptors: Locations &
Functions
M1 M2 M3
• Autonomic ganglia:
depolarization
• Gastric glands:
increased secretion
• CNS: learning,
memory, motor
function
• Heart: Decrease
rate, force
• CNS: tremor,
analgesia
• Visceral smooth
muscle: contraction
• Visceral smooth muscle:
contraction
• Iris: constriction of pupil
• Ciliary muscle: contraction
• Exocrine glands: secretion
• Vascular endothelium:
vasodilatation

7. Nicotinic Cholinoceptors
NM NN
• Neuromuscular
junction: contraction
of skeletal muscle
• Autonomic ganglia:
depolarization
• Adrenal medulla:
catecholamine release
• CNS: site specific action

8. CholinergicTransmission

9. Cholinergic/Parasympathomimetic Drugs
Cholinergic Agonists Anti-cholinesterases
Choline esters Alkaloids Reversible Irreversible
Acetylcholine Pilocarpine Carbamates: Physostigmine,
Neostigmine,
Pyridostigmine,
Edrophonium, Rivastigmine,
Donepezil, Galantamine
Carbamates:
Carbaryl, Propoxur
Methacholine Arecoline Organophosphates:
Dyflos,
Echothiophate,
Malathion, Diazinon,
Tabun, Sarin, Soman
Carbachol Muscarine
Bethanechol Acridine:Tacrine

10. MuscarinicActions of CholinergicAgonists (ACh)
Organ Receptor
Involved
Mechanism Effect
Heart M2 Hyperpolarization of SA Node
Increased Refractory Period at AV
node and His-Purkinje Fibres
Bradycardia, cardiac arrest,
Delayed conduction, Prolonged
P-R interval, Heart Block
Blood
Vessels
Nitric Oxide(NO) release:
Vasodilation
Fall in BP, flushing
M3 Vasoconstriction
NO – dilatation of cavernous
sinus
Erection of penis

11. MuscarinicActions of Cholinergic Agonists (ACh)
Organ Receptor
Involved
Mechanism Effects
Smooth
Muscle
M3 + M2 Increased tone and peristalsis
of GIT, sphincters relaxed
Abdominal cramps, evacuation of
bowels
M3 Increased peristalsis in
ureters, detrusor contracts,
trigone & sphincter relaxes
Voiding of bladder
M3 Constriction of bronchial
muscles
Bronchospams, dyspnoea,
asthamatic attack

12. MuscarinicActions of Cholinergic Agonists (ACh)
Organ
Receptor
Involved
Mechanism Effects
Glands M3 + M2 Increased secretion Salivation, sweating, lacrimation,
increased tracheobronchial and gastric
secretions
Eyes M3
Contraction of circular
muscle of iris
Miosis
Contraction of ciliary
muscle
Blurring of near vision, increased
aqueous outflow, decreased intra ocular
pressure in glaucomatous eye

13. Nicotinic Actions of Cholinergic Drugs (ACh)
Organ Receptor Involved Mechanism & Effects
Autonomic
Ganglia
NN • Stimulation at higher doses
Skeletal
Muscles
NM
• Contraction of muscle fibres
• Intra-arterial injection: twitching and
fasciculations

14. Choline esters: Uses and Side Effects
•Uses:
•Rarely used (evanescent
and non selective
action)
•Bethanechol: non-
obstructive urinary
retention, neurogenic
bladder
•Side effects:
•Belching, colic
•Involuntary
urination/defecation
•Flushing, sweating
•Fall in BP
•Bronchospasm

15. Cholinomimetic Alkaloids:Pilocarpine
•Prominent muscarinic actions; ganglionic action via M1
receptors
•Dose dependentCVS Effects
•Eyes:
•Local application – penetrates cornea, miosis, ciliary
muscle contraction, fall in intraocular tension (M3)
•Use: as miotics
•S/E: marked sweating, salivation, increased secretions

16. Cholinomimetic Alkaloids
Arecholine
• Source: betel nut Areca
catechu
• Muscarinic as well as
Nicotinic actions
• No therapeutic use
Muscarine
• Source: mushrooms Amanita
muscaria, Inocybe sps.
• Only muscarinic actions
• Not used therapeutically, has
toxicological importance

17. Anti-cholinesterases (AChE)
•Inhibits Cholinesterase (ChE)  protects ACh from
hydrolysis (Amplification of endogenous ACh) 
Cholinergic effects
•Additional direct action on Nicotinic receptors

18. AChE: PharmacologicalActions
Characteristics
(Example)
Muscarinic
Nicotinic
CNS
Ganglia
Skeletal
Muscle
Lipid soluble
(Physostigmine,
organophosphates)
+++ + Less
prominent
+++
Lipid insoluble
(Neostigmine)
Less
prominent
+ +++ none

19. AChE: PharmacologicalActions
• Skeletal Muscles: twitching and fasciculations at low dose,
weakness and paralysis at high dose
• Prolonged action of ACh on motor end plates and prejunctional
fibres twitching and fasciculations
• High dose: persistent depolarization  neuromuscular
transmission blockade  weakness and paralysis
• Ganglia: stimulation at low dose, blockade at high dose
• CVS: complex, unpredictable effects
• CNS: general arousal at low dose, excitement, confusion at high
dose

20. AChE: Pharmacokinetics
•Physostigmine:
• Rapid absorption (oral,
parenteral, topical in eye)
• Crosses BBB, central effects
• Metabolism by hydrolysis
•Organophosphates:
• Absorbed from all sites
• Hydrolysed and oxidised and
then excreted
•Neostigmine:
• Poor oral absorption (20-30
times parenteral dose)
• Does not cross BBB, cornea
• Partially hydrolysed and
partially excreted unchanged
in urine

21. AChE: Uses
As Miotic
•Glaucoma:
•Pilocarpine - rapid and short lasting (4-6hrs)
• S/E: diminution of vision especially in dim light, spasm of
accommodation, brow pain; nausea, diarrhoea, sweating,
bronchospasm with higher concentration
•Physostigmine 0.1% - supplement pilocarpine
•Reversal of mydriasis after refraction
•Prevent/break adhesions: In conjunction with mydriatics

22. AChE:Uses
•Myasthenia gravis(MG)
• Treatment
•Neostigmine
• 15 mg orally 6 hourly
• Adjusted according to response
• Dose requirement fluctuates
•Pyridostigmine
•DiagnosticTests
• AmeliorativeTest: Inj
Edrophonium 2mg i.v. (test dose)
followed by 8 mg i.v. after 30-60
sec. reversal of weakness and
short lasting improvement of
strength: +ve for MG
• ProvocativeTest

23. AChE: Uses
• Post-operative paralytic ileus/urinary retention: Inj. Neostigmine 0.5-1 mg s.c.
• Post-operative decurarization: Neostigmine 0.5-2 mg i.v. preceeded by atropine to block
muscarinic effects  rapidly reversal of muscle paralysis induced by competitive
neuromuscular blockers
• Cobra bite: Neostigmine + Atropine to prevent respiratory paralysis
• Belladona poisoning/Dhatura poisoning: Physostigmine 0.5-2 mg i.v. repeat as required
(S/E – hypotension, arrhythmia, undesireable central effects: last resort), Neostigmine
safer
• Drug Overdose:TCA, phenothiazines, antihistaminics – Physostigmine (rare)
• Alzheimer’s Disease: cerebroselective AChE (rivastigmine, donepezil, galantamine)

24. •That will be all for today
•Please revise the topic….
•Next class: Anticholinergics Drugs