The seminar discusses cholinergic drugs, which affect the autonomic nervous system and are classified into muscarinic and nicotinic receptors based on their action. Key topics include the synthesis and release of acetylcholine, types of cholinergic agents, and their physiological effects, along with clinical applications in conditions such as glaucoma and myasthenia gravis. The document also covers the structure and modifications of these drugs, as well as references for further reading.

1. Seminar on Cholinergic DrugsSeminar on Cholinergic Drugs
(Medicinal chemistry)(Medicinal chemistry)
Guided ByGuided By : Mr.P.Prasanna Raja: Mr.P.Prasanna Raja
Presented ByPresented By : B.Bharath kumar: B.Bharath kumar

2. IntroductionIntroduction
• Drugs affecting the ANS are divided intoDrugs affecting the ANS are divided into
two groups . According to the type oftwo groups . According to the type of
neurons involved in their mechanism ofneurons involved in their mechanism of
actionaction
Cholinergics – Acts on the receptors stimulatedCholinergics – Acts on the receptors stimulated
by Achby Ach
Adrenergics - Acts on the receptors stimulatedAdrenergics - Acts on the receptors stimulated
by Norepinephrineby Norepinephrine

3. Cholinergic agentsCholinergic agents
• Cholinergic agents are the drugs that eitherCholinergic agents are the drugs that either
directly or indirectly produce effect similar todirectly or indirectly produce effect similar to
those elicited by Acetylcholinethose elicited by Acetylcholine
• Dale while studying the pharmacological actionsDale while studying the pharmacological actions
of Ach distinguished two types of activities whichof Ach distinguished two types of activities which
he designated as muscarinic and nicotiniche designated as muscarinic and nicotinic

4. Synthesis of AchSynthesis of Ach
• Choline is taken up into the nerve terminals byCholine is taken up into the nerve terminals by
special choline transport system mediated by aspecial choline transport system mediated by a
carrier that cotransports sodium.carrier that cotransports sodium.
• The choline transport appears to be the rateThe choline transport appears to be the rate
limiting steplimiting step
• It can be inhibited by hemicholinium.It can be inhibited by hemicholinium.
• The choline is acetylated by the enzyme cholineThe choline is acetylated by the enzyme choline
acetyl transferase to form Ach The acetyl groupacetyl transferase to form Ach The acetyl group
source is acetyl-coAsource is acetyl-coA

5. Storage and Release of achStorage and Release of ach
• The Ach is packaged into vesicles by an active transport processThe Ach is packaged into vesicles by an active transport process
coupled with the efflux of protonscoupled with the efflux of protons
• The mature vesicles also contain ATP and ProteoglyconThe mature vesicles also contain ATP and Proteoglycon
• When an action potential propagated voltage sensitive calciumWhen an action potential propagated voltage sensitive calcium
channels in the presynaptic membrane opens causes anchannels in the presynaptic membrane opens causes an
intracellular increase in calcium.intracellular increase in calcium.
• Elevated calcium levels promote the fusion of synaptic vesicles withElevated calcium levels promote the fusion of synaptic vesicles with
the cell membrane and release of their contents into the synapticthe cell membrane and release of their contents into the synaptic
cleft.cleft.
• This release can be blocked by botulinum toxin.This release can be blocked by botulinum toxin.
• Ach is degraded by acetylcholinesterase and forms choline andAch is degraded by acetylcholinesterase and forms choline and
acetate in the synaptic cleft.acetate in the synaptic cleft.

7. CholinoceptorsCholinoceptors
• Cholinergic receptors have been characterized as nicotinic and muscarinicCholinergic receptors have been characterized as nicotinic and muscarinic
on the basis of their ability to be bound by naturally occuring alkaloidson the basis of their ability to be bound by naturally occuring alkaloids
nicotine and muscarine respectivelynicotine and muscarine respectively
NICOTINIC RECEPTORSNICOTINIC RECEPTORS
• It is a ligand gated cationic channelIt is a ligand gated cationic channel
• It is stimulated by nicotine and blocked by d-tubocurarine orIt is stimulated by nicotine and blocked by d-tubocurarine or
hexamethonium.hexamethonium.
• It is of two typesIt is of two types
 N1N1: It is located at skeletal muscle end plate: It is located at skeletal muscle end plate
(neuro muscular junction ) .(neuro muscular junction ) .
It causes depolarisation of muscle end plate and contraction of skeletal muscles.It causes depolarisation of muscle end plate and contraction of skeletal muscles.
Agonist-nicotine,PTAAgonist-nicotine,PTA
Antagonist-tubocurarineAntagonist-tubocurarine
 N2 :N2 :IIt is located at atonomic ganglia (depolarisation), adrenal medulla ( catecholt is located at atonomic ganglia (depolarisation), adrenal medulla ( catechol
release )and cns.release )and cns.
Agonist-hexamethonium.Agonist-hexamethonium.

8. Muscarinic receptorsMuscarinic receptors
• M1M1:Neuronal receptors located on ganlion cells , cortex ,:Neuronal receptors located on ganlion cells , cortex ,
hippocampus and corpus striatum.hippocampus and corpus striatum.
Antagonist : pirenzepineAntagonist : pirenzepine
Agonist : oxotremorineAgonist : oxotremorine
Functions : learning , salivary secretions , memory , motorFunctions : learning , salivary secretions , memory , motor
functions .functions .
• M2M2 : Cardiac receptors: Cardiac receptors
Agonist : methacholineAgonist : methacholine
Antagonist : methoctramineAntagonist : methoctramine
Functions : vagal bradicardia, auto receptorsFunctions : vagal bradicardia, auto receptors
• M3M3 : It causes vasodilation through EDRF and smooth muscle: It causes vasodilation through EDRF and smooth muscle
contractioncontraction
 All the muscarinic receptors are G-protein couple receptors can beAll the muscarinic receptors are G-protein couple receptors can be
blocked by atropine .blocked by atropine .

9. ClassificationClassification
cholinergic agonistscholinergic agonists
• Choline estersCholine esters
Acetyl cholineAcetyl choline
MethacholineMethacholine
CarbacholCarbachol
BethanecholBethanechol
• AlkaloidsAlkaloids
MuscarineMuscarine
PilocarpinePilocarpine
ArecolineArecoline

11. AnticholinesterasesAnticholinesterases
ReversibleReversible IrreversibleIrreversible
CarbamatesCarbamates AcridineAcridine OrganophosphaOrganophospha
testes
carbamatescarbamates
PhysostigminePhysostigmine
NeostigmineNeostigmine
edrophonium,edrophonium,
TacrineTacrine DyflosDyflos
EcothiophateEcothiophate
ParathionParathion
TabunTabun
CarbarylCarbaryl

13. SARSAR
• structure of achstructure of ach
Modification of Quaternary Ammonium GroupModification of Quaternary Ammonium Group
 Methyl groups substituted with higher alkyl groups are inactive as agonistMethyl groups substituted with higher alkyl groups are inactive as agonist
 If all methyl groups are ethylated it shows antagonistic activityIf all methyl groups are ethylated it shows antagonistic activity
 The positive charge is necessary for its activityThe positive charge is necessary for its activity
 If all methyl groups are replaced by H ion it losts its activityIf all methyl groups are replaced by H ion it losts its activity

14. Modification of ethylene bridgeModification of ethylene bridge
 Introduction of alkyl group will rapidly reduce activityIntroduction of alkyl group will rapidly reduce activity
 Rule of five : Ing postulated that there should not beRule of five : Ing postulated that there should not be
more than five atoms between nitrogen and the terminalmore than five atoms between nitrogen and the terminal
hydrogen atom for maximal activityhydrogen atom for maximal activity
 Introduction of methyl group on the beta carbon formsIntroduction of methyl group on the beta carbon forms
methacholinemethacholine
 Introduction of methyl group on alpha carbon will leads toIntroduction of methyl group on alpha carbon will leads to
less active compoundless active compound
 Addition of one or two ethyl groups will form chiralAddition of one or two ethyl groups will form chiral
moleculesmolecules

15. Modification of acloxy groupModification of acloxy group
• As predicted by the rule of five If the acetylAs predicted by the rule of five If the acetyl
group is replased by higher homologues thegroup is replased by higher homologues the
resulting esters are less potent and instead theyresulting esters are less potent and instead they
have antagonistic activityhave antagonistic activity
• The esters derived from carbamic acid areThe esters derived from carbamic acid are
referred to as carbamates and they are morereferred to as carbamates and they are more
stable than carboxylate esters to hydrolysisstable than carboxylate esters to hydrolysis
Ex: carbacholEx: carbachol
• Carbachol is less hydrolyzed by AchE, gastricCarbachol is less hydrolyzed by AchE, gastric
acid and butyryl cholinesterase so it can beacid and butyryl cholinesterase so it can be
given orallygiven orally

16. PilocarpinePilocarpine
• StructureStructure
• preparationpreparation: The alkaloid is extracted from leaves of P.microphyllus with alcohol: The alkaloid is extracted from leaves of P.microphyllus with alcohol
and Hcl .the solvents is evaporated and residue is treated with ammonia the acquousand Hcl .the solvents is evaporated and residue is treated with ammonia the acquous
filtrate isbasified with strong ammonia. Then treated with chloroform and the solventfiltrate isbasified with strong ammonia. Then treated with chloroform and the solvent
is distilled and add dil. Nitric acid and allow to crystalliseis distilled and add dil. Nitric acid and allow to crystallise
• UsesUses : It is a non selective agonist and acts on all muscarinic receptors mainly on: It is a non selective agonist and acts on all muscarinic receptors mainly on
M3 and causes smooth muscles to contract in gut,trachea and eyeM3 and causes smooth muscles to contract in gut,trachea and eye
In eye it produces pupillary constriction and spasm of accomidationIn eye it produces pupillary constriction and spasm of accomidation
(cycloplegia)(cycloplegia)
The pupillary constriction and spasm of accomidation will reduce intraThe pupillary constriction and spasm of accomidation will reduce intra
ocular tension by establishing better drianage of occular fluid through theocular tension by establishing better drianage of occular fluid through the
canal of schlemm so used in treatment of glaucomacanal of schlemm so used in treatment of glaucoma

17. CarbacholCarbachol
• StructureStructure
• Ethanaminium 2-[(aminocarbonyl) oxy]- N, N, N-Ethanaminium 2-[(aminocarbonyl) oxy]- N, N, N-
trimethyl-chloridetrimethyl-chloride

18. CarbacholCarbachol
• SYNTHESISSYNTHESIS
 Properties : Faintly yellow crystalline ,hygroscopic powderProperties : Faintly yellow crystalline ,hygroscopic powder
Melts at 200 to 204 degreesMelts at 200 to 204 degrees
Pka : 4.8

19. Uses of CarbacholUses of Carbachol
• Narrow angle glaucomaNarrow angle glaucoma
• To induce miosis prior to occularTo induce miosis prior to occular
surgerysurgery
• It is less suceptible to hydrolysis so itIt is less suceptible to hydrolysis so it
is more stable in aqueous solutionis more stable in aqueous solution

20. CONCLUSIONCONCLUSION
• The cholinergic drugs are the drugs thatThe cholinergic drugs are the drugs that
mimics the actions of the parasympatheticmimics the actions of the parasympathetic
system and used in treating manysystem and used in treating many
diseases like glaucoma , xerostomia ,diseases like glaucoma , xerostomia ,
myasthenia gravis etcmyasthenia gravis etc

21. REFERENCESREFERENCES
1) Text book of Medicinal chemistry by William O1) Text book of Medicinal chemistry by William O
Foye,Lea febiger, PhiladelphiaFoye,Lea febiger, Philadelphia
2) wilson and giswolds organic Medicinal2) wilson and giswolds organic Medicinal
Chemistry and Pharmaceutical chemistry by J HChemistry and Pharmaceutical chemistry by J H
Block and J M BealeBlock and J M Beale
3) S.N.Pandeya text book of medicinal chemistry3) S.N.Pandeya text book of medicinal chemistry
4) Text book of Pharmacology by Rang and Dale4) Text book of Pharmacology by Rang and Dale