Académique Documents
Professionnel Documents
Culture Documents
Presentation
By
Dr.RAJIN
Chair:Dr.Anil Prabhakaran
Structure
Pathways
Receptors
Clinical considerations
HISTORY
Acetylcholine (ACh) was first identified in
the year 1914 by Henry Hallett Dale for
its actions on heart tissue.
It was confirmed as a neurotransmitter
by Otto Loewi who initially gave it the
name vagusstoff because it was released
from the vagus nerve. Both received the
1936 Nobel Prize in Physiology or
Medicine for their work.
Acetylcholine was also the
firstneurotransmitter to be identified
MOLECULAR STRUCTURE
CH3 O
CH3
Acetylcholine is an ester of acetic
acid and choline with chemical
formula CH3COOCH2CH2N+(CH3)3. This structure is
reflected in the systematic name, 2-acetoxy-N,N,N-
trimethylethanamine
Acetyl.CoA
+
choline
ACh
choline
ACh
ASE
Postsynaptic tissue
Cholinergic neurons
within CNS Outside CNS
Nu. basalis of
Medial septal
MEYNERT nucleus
Horiz. & vert.
Diagonal bands of
BROCA
Areas of cortex
&
Ant, cingulale hippocampus
amygdala
Gyrus &
Olfactory bulb
Mesopontine complex
Pedunculopontine &
Laterodorsal tegmental nu.
of midbrain & pons
5. M5 forming homomeric
receptors
M1 receptor
Gq protein coupled
Increases phosphatidine inositol
turnover
Location: forebrain including cortex,
hippocampus, striatum
Functions: memory ( involving
interaction between cortex &
hippocampus)
: seizures
M2 receptors
Gi protein coupled .
Decreases adenylate cyclase
Location: heart,brain
Functions: mediates tremor,
hypothermia & analgesia induced by
muscarinic receptors
M3 receptor
Gq protein coupled
Increases phosphatidine inositol
turnover
Location: smooth muscles of GIT &
GUT, salivary glands,many areas of
CNS
Functions: no major role in CNS
M4 receptors
Gi protein coupled
Decreases adenylate cyclase
Location: hippocampus, cortex,
striatum, thalamus, cerebellum
Functions: opposes the effects of D1
receptors in the striatum
M5 receptors
Gq protein coupled
Increases phosphatidine inositol
turnover
Location: peripheral & cerebral blood
vessels
Functions: ? Mediate cholinergic
cerebral arterial vasodilation
NICOTINIC RECEPTORS
Ligand gated ion channel
Cholinergicagents such as
physostigmine is effective in delirium
of all causes
ALZHEIMER’S DISEASE
Impdrug interactions:
DRA, MAO-I, tricyclics
Uses
Neuroleptic induced parkinsonism,
neuroleptic induced dystonia,
akathesia
.,
CHOLINESTERASE INHIBITORS
Tacrine
Inhibits AChE 120–160 mg, divided four
times daily 30% elevated transaminases and
severe GI intolerance.
Donepezil
Inhibits AChE 5–10 mg every day.
May be associated with insomnia. Fewer GI
symptoms
.Rivastigmine
Inhibits butyryl cholinesterase
and AChE 6–12 mg, divided b.i.d. Gradual
titration may decrease GI side effects.
Galantamine
Allosteric modulation of nicotinic
receptors, weaker AChE inhibition 24–32 mg,
divided b.i.d. Gradual titration may decrease
GI side effects. Least induction of AChE.
Should be used cautiously with
succinyl choline
Uses
: treat cognition impairment in
Alzheimers dementia
:vascular dementia
:traumatic brain injury
:parkinsons diseases
Varenicline
alpha4beta2 nicotinic acetylcholine
receptor partial agonist developed from
cytisine, a drug widely used in central and
eastern Europe for smoking cessation
Nicotine receptor partial agonists may help
smokers to quit by a combination of
maintaining moderate levels of dopamine to
counteract withdrawal symptoms (acting as
an agonist) and reducing smoking satisfaction
(acting as an antagonist). Nicotine receptor partial agonists for
smoking cessation.Cochrane Database Syst Rev. 2008 Jul 16; (3):CD006103. Epub 2008 Jul 16.
[Cochrane Database Syst Rev. 2008
Direct acting
Bethanechol
Carbachol
Cevimeline
Pilocarpine
Suberylcholine
Reversible
The following substances reversibly inhibit the
enzyme acetylcholinesterase
Alzheimer's disease (Donepezil ,Galantamine,
Rivastigmine,Tacrine ,
Edrophonium (myasthenic and cholinergic crisis)
Neostigmine (myasthenia gravis)
Physostigmine(in glaucoma and anticholinergic drug
overdoses)
Pyridostigmine(myasthenia gravis)
Carbamate(insecticides)
Irreversible
Semi-permanently inhibit the enzyme
acetylcholinesterase.
Echothiophate ,
Isofluorophate ,
Organophosphate ,Insecticides ,Malathion
,Parathion ,Azinphos methyl, Chlorpyrifos
Organophosphate-containing nerve agents (e.g.,
Sarin)
Victims of organophosphate-containing
nerve agents commonly die of
suffocation as they cannot relax their
Thoracic diaphragm
Reactivation of acetylcholine
esterase==== Pralidoxime
ACh receptor antagonists
====Antimuscarinic agents====
Atropine
Ipratropium
Scopolamine
Tiotropium
Ganglionic blocker
Mecamylamine
Hexamethonium
Nicotine (in high doses)
Trimethaphan
Neuromuscular blockers
Atracurium ,Cisatracurium ,Doxacurium ,
Metocurine ,Mivacurium ,Pancuronium
,Rocuronium ,Succinylcholine ,Tubocurarine,
Vecuronium
Release isnhibitor
Botulism toxin Botulin acts by suppressing
the release of acetylcholine.
References:
Comprehencive test book of
psychiatry 8th Ed
Essential psychopharmacology by
Stephen.M.Stahl 3rd Ed
Synopsis of psychiatry 10th Ed
Wikipedia net sources
THANK YOU