CLASS - 2

CHOLINERGIC
NERVOUS SYSTEM

DR. LAXMIKANTA SAY
HISTORY
• 1977 – Fambrough, Devreotes and
Card
- Chemically isolated by detergents
- Nicotinic ACh receptors are
hydrophob...
CHOLINERGIC TRANSMISSION
1.

All preganglionic autonomic nerve
(sympathetic & parasympathetic ).

ending

2.Postganglionic...
CHOLINERGIC TRANSMISSION
• Ach - synthesized in the terminal endings &
varicosities of cholinergic nerve fibre.
• Synthesis:
Acetyl-CoA + Choline

AcetylCholine

Choline acetyl transferase

• Destruction:
Acetylcholine

Choline + Acet...
Biochemical events at a cholinergic sysnapse
Types of Ach - esterase
Acetlycholine esterase/
True choline esterase

Pseudocholine
esterase

1. Distribution

Found in p...
Types of Cholinergic Receptors
• Muscarinic action :
- Ach acts like muscarine
- an alkaloid from poisonous
mushroom “Aman...
Muscarinic Receptors
• site: all effector cells stimulated by

postganglionic cholinergic neurons of
Parasympathetic /symp...
M1
• Location: Autonomic ganglia, Gastric glands, CNS
• Function:
- Depolarization
- Histamine release, acid secretion
- L...
M2
• Location: Heart (SAN, AVN, Atrium, Ventricle),

Cholinergic nerve endings, Visceral smooth muscles

• Function:
-Hear...
M3
• Location: Visceral smooth muscle, Iris, Ciliary
muscle, Exocrine gland, Vascular endothelium

• Function:
- Smooth mu...
• Activation: Ach, Muscarine
• Effects
- Heart –Inhibitory effect, H.R, Conduction in AVN
- Smooth Muscle & Glands - Excit...
Nicotinic Receptors
• Location: - Autonomic ganglia
- Neuromuscular junction
- Central nervous system
- Adrenal Medulla
• ...
• Activation – Acetylcholine, Nicotine
• Effect – Excitation
• Blockade :
- Ganglion blockers
(block nicotinic receptors f...
NM

NN

1. Location
& Function
suserved

•NM Junction:
depolarization of muscle
end plate – contraction of
skeletal muscle...
DRUGS
• 1. Cholinomimetic or
parasympathomimetic
• 2. Anticholinesterases
• 3. Anticholinergic or
Parasympatholytic
Cholinomimetic
or
Parasympathomimetic
• Drugs producing similar actions that of
ACh, either
• “directly interacting with C...
Cholinergic Agonist

(Drugs acting on Cholinergic Effector Organs)
• Choline esters
- Acetylcholine
- Methacholine
- Carba...
Anticholinesterase

Anti-ChEs are agents inhibits ChE, protect ACh
from hydolysis.
• Reversible
• Irreversible
- Physostig...
Anticholinergics or Parasympatholytic
• 1.Natural Alkaloids
- Atropine, Hyoscine(Scopolamine)
• 2. Semisynthetic deraivati...
Cont..

• 3. Synthetic compounds
(a) Mydriatics: Cyclopentolate, Tropicamide
(b) Antisecretory-antispasmodics:
- Propanthe...
APPLIED
Glaucoma
Myasthenia gravis
Alzheimer’s disease
Anticholinesterase poisoning
THANK YOU
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Class 2, cholinergic

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Class 2, cholinergic

  1. 1. CLASS - 2 CHOLINERGIC NERVOUS SYSTEM DR. LAXMIKANTA SAY
  2. 2. HISTORY • 1977 – Fambrough, Devreotes and Card - Chemically isolated by detergents - Nicotinic ACh receptors are hydrophobic glycoprotein
  3. 3. CHOLINERGIC TRANSMISSION 1. All preganglionic autonomic nerve (sympathetic & parasympathetic ). ending 2.Postganglionic neurons of Parasympathetic 3.Post ganglionic sympathetic ending innervating Sweat glands ,Piloerector muscles of hair, blood vessels. 4. NM Junction 5.Parts of Brain –Cerebral Cortex, thalamus, forebrain nuclei
  4. 4. CHOLINERGIC TRANSMISSION • Ach - synthesized in the terminal endings & varicosities of cholinergic nerve fibre.
  5. 5. • Synthesis: Acetyl-CoA + Choline AcetylCholine Choline acetyl transferase • Destruction: Acetylcholine Choline + Acetate ion Acetylcholine esterase
  6. 6. Biochemical events at a cholinergic sysnapse
  7. 7. Types of Ach - esterase Acetlycholine esterase/ True choline esterase Pseudocholine esterase 1. Distribution Found in place where Ach is naturally found, e.g, Neuromuscular junction, ganglion synapses , Gray matter and RBC Plasma, Liver, Intestine, White matter 2. Hydrolysis Very Fast Slow 3. Inhibition More sensitive to Physostigmine More sensitive to Organophosphate 4. Function Termination of ACh action Hydrolysis of ingested esters
  8. 8. Types of Cholinergic Receptors • Muscarinic action : - Ach acts like muscarine - an alkaloid from poisonous mushroom “Amanita muscaria” • Nicotinic action : - activates only nicotinic receptors
  9. 9. Muscarinic Receptors • site: all effector cells stimulated by postganglionic cholinergic neurons of Parasympathetic /sympathetic N S. • Types • • • • • M1– brain, autonomic ganglia M2 – heart M3 – glands & smooth muscle M4 – CNS M5 - CNS
  10. 10. M1 • Location: Autonomic ganglia, Gastric glands, CNS • Function: - Depolarization - Histamine release, acid secretion - Learning, memory, motor functions • Nature – G-protein coupled, 7-TM • Transducer mechanism: - IP3/DAG- Cytosolic Ca2+ - PLA2 - PG synthesis • Agonist: MCN-343A, Oxotremorine • Antagonist: Pirenzepine,Telenzepine
  11. 11. M2 • Location: Heart (SAN, AVN, Atrium, Ventricle), Cholinergic nerve endings, Visceral smooth muscles • Function: -Heart: Hyperpolarization, rate of impulse generation, velocity of conduction & contractility - Cholinergic nerve ending: ACh release - CNS: tremor, analgesia - Visceral smooth muscle: contraction • • • • Nature:G-protein coupled, 7-TM Transducer mechanism: K+ channel opening, cAMP Agonist: Methacoline Antagonist: Methoctramine, Tripitramine
  12. 12. M3 • Location: Visceral smooth muscle, Iris, Ciliary muscle, Exocrine gland, Vascular endothelium • Function: - Smooth muscle contraction, Exocrine gland secretion - Vascular endothelium: Vasodilatation (release of NO) • Nature – G-protein coupled, 7-TM • Transducer mechanism: - IP3/DAG- Cytosolic Ca2+ - PLA2 - PG synthesis • Agonist: Bethanechol • Antagonist: Hexahydrosiladifenidol, Darifenacin
  13. 13. • Activation: Ach, Muscarine • Effects - Heart –Inhibitory effect, H.R, Conduction in AVN - Smooth Muscle & Glands - Excitatory effect • Blockage – atropine • Mechanism of Action - Heart SA Node – inhibition of adenyl cyclase, leads to opening of K+ channels, slowing of spontaneous depolarization, & H.R. - Smooth muscle & glands – IP3 & intracellular Ca2+
  14. 14. Nicotinic Receptors • Location: - Autonomic ganglia - Neuromuscular junction - Central nervous system - Adrenal Medulla • Nature: - Ligand gated ion channels • Mode of action:- quick in onset & brief in duration
  15. 15. • Activation – Acetylcholine, Nicotine • Effect – Excitation • Blockade : - Ganglion blockers (block nicotinic receptors for Ach in autonomic ganglia but not at NM-junction) e.g, hexamethonium, trimethophan • Mechanism of Action - When stimulated the channel opens, permits Na+ & other cations producing Depolarisation
  16. 16. NM NN 1. Location & Function suserved •NM Junction: depolarization of muscle end plate – contraction of skeletal muscle •Autonomic Ganglia: depolarization – postganglionic impulse •Adrenal Medulla: catecholamine release •CNS: site specific excitation or inhibition 2. Nature Intrinsic ion channel, pentamer α2β ε or y & δ subunits Intrinsic ion channel, pentamer of only αβ subunits 3. Transducer mechanism Opening of Cation (Na+, K+) channels Opening of Cation (Na+, K+, Ca2+) channels 4. Agonist PTMA (Phenyl trimethyl ammonium), Nicotine DMPP (Dimethyl phenyl piperazinum, Nicotine 5.Antagonist Tubocurarine, α-Bungarotoxin Hexamethonium, Trimethaphan
  17. 17. DRUGS • 1. Cholinomimetic or parasympathomimetic • 2. Anticholinesterases • 3. Anticholinergic or Parasympatholytic
  18. 18. Cholinomimetic or Parasympathomimetic • Drugs producing similar actions that of ACh, either • “directly interacting with Cholinergic receptors (cholinergic agonist) “ or • “increasing availability of ACh at these sites (anticholine esterases)”
  19. 19. Cholinergic Agonist (Drugs acting on Cholinergic Effector Organs) • Choline esters - Acetylcholine - Methacholine - Carbachol - Bethanecol • Alkaloids - Muscarine - Pilocarpine - Arecoline
  20. 20. Anticholinesterase Anti-ChEs are agents inhibits ChE, protect ACh from hydolysis. • Reversible • Irreversible - Physostigmine - Dyflos - Neostigmine - Echothiophate - Pyridostigmine - Parathion* - Edrophonium - Malathion* - Rivastigmine - Diazinon* - Donepezil - Tabun - Galantamine - Sarin - Tacrine - Soman
  21. 21. Anticholinergics or Parasympatholytic • 1.Natural Alkaloids - Atropine, Hyoscine(Scopolamine) • 2. Semisynthetic deraivatives - Homatropine, - Atropine methonitrate, - Hyoscine butyl bromide, - Ipratropium bromide, - Tiotropium bromide,
  22. 22. Cont.. • 3. Synthetic compounds (a) Mydriatics: Cyclopentolate, Tropicamide (b) Antisecretory-antispasmodics: - Propantheline, Oxyphenonium, Clidinum, Glycopyrolate, Isopropamide - Dicyclomine, Valethamete, Pirenzepine (c) Vasoselective: Oxybutynin, Flavoxate, Tolterodine (d) Antiparkinsonian: Trihexiphenidyl (Benzohexol), Procyclidine, Biperiden
  23. 23. APPLIED Glaucoma Myasthenia gravis Alzheimer’s disease Anticholinesterase poisoning
  24. 24. THANK YOU
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