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Drugs acting on parasympathetic nervous system 1
1. CHOLINERGICS, ANTICHOLINERGICS
& ANTICHOLINESTERASES
Part 1: Cholinergic & anticholinesterases
Mr. Somdatta Y Chaudhari
Dept. of Pharm. Chemistry
P.E.S. Modern College of Pharmacy, Nigdi
P.E.S. Modern College of Pharmacy, Nigdi 1
2. Contents
Part 1: Cholinergics & anticholinesterases
1. Nerve Transmission (3 slides)
2. Neurotransmitter
3. Transmission process (10 slides)
4. Cholinergic receptors (2 slides)
4.1. Nicotinic receptor (2 slides)
4.2. Muscarinic receptor - G Protein coupled receptor (2 slides)
5. Cholinergic agonists
5.1. Acetylcholine as an agonist
5.2. Nicotine and muscarine as cholinergic agonists
5.3. Requirements for cholinergic agonists
6. SAR for acetlcholine (6 slides)
7. Binding site (muscarinic) (3 slides)
8. Active conformation of acetylcholine (2 slides)
9. Instability of acetylcholine
10. Design of cholinergic agonists (7 slides)
11. Uses of cholinergic agonists (2 slides)
P.E.S. Modern College of Pharmacy, Nigdi 2
4. 1. Nerve Transmission
Peripheral nervous system
Peripheral nerves
Muscle
Gastro-
intestinal
tract
(GIT)
Brain
Spinal cord
CNS
Heart
P.E.S. Modern College of Pharmacy, Nigdi 4
5. Sympathetic nervous system = ‘Fight or Flight Response’
Parasympathetic nervous system = ‘Rest and Digest Response’
P.E.S. Modern College of Pharmacy, Nigdi 5
6. 1. Nerve Transmission
Peripheral nervous system
CNS
(Somatic)
CNS
(Autonomic)
Sympathetic
Parasympathetic
NA
Ach
(N)
Synapse
Ach (N)
Ach
(N)
Ach
(N)
Ach
(M)
Adrenal
medulla
Adrenaline
Skeletal
muscle
Synapse
AUTONOMIC
Smooth muscle
Cardiac muscle
P.E.S. Modern College of Pharmacy, Nigdi 6
13. Overview of the ACh Neurotransmitter System:
Release, Action, Uptake, Synthesis and
Degradation of ACh
P.E.S. Modern College of Pharmacy, Nigdi 13
14. 3. Transmission process
Signal in nerve 1
Acetylcholinesterase enzyme
Cholinergic receptor
. Acetylcholine
Vesicle
...
...
...
Nerve 1
Nerve 2
Signal
P.E.S. Modern College of Pharmacy, Nigdi 14
15. 3. Transmission process
Vesicles fuse with membrane and release Ach
Nerve 1
Nerve 2
Signal
P.E.S. Modern College of Pharmacy, Nigdi 15
17. Nerve 2
3. Transmission process
• Receptor binds Ach
• Induced fit triggers 2o message
• Triggers firing of nerve 2
• Ach undergoes no reaction
2o Message
P.E.S. Modern College of Pharmacy, Nigdi 17
18. 3. Transmission process
• Ach departs receptor
• Receptor reverts to resting state
• Ach binds to acetylcholinesterase
Nerve 2
P.E.S. Modern College of Pharmacy, Nigdi 18
19. 3. Transmission process
Ach hydrolysed
by acetylcholinesterase
Nerve 2
Acetylcholine
H3C
C
O
O
Choline
+ NMe3
C
O
H3C OH
Acetic acid
NMe3
HO
P.E.S. Modern College of Pharmacy, Nigdi 19
20. 3. Transmission process
Choline binds to carrier protein
Carrier protein for choline
Nerve 1
Nerve 2
Choline
P.E.S. Modern College of Pharmacy, Nigdi 20
22. 3. Transmission process
Ach resynthesised
Nerve 1
Nerve 2
E1
Choline
+ CH2 NMe3CH2HO
C
O
H3C SCoA
Acetylcholine
H3C
C
O
O
NMe3
E 1 = Choline acetyltransferase
P.E.S. Modern College of Pharmacy, Nigdi 22
23. 3. Transmission process
Ach repackaged in vesicles
Nerve 1
Nerve 2
P.E.S. Modern College of Pharmacy, Nigdi 23
24. 4. Cholinergic receptors
Receptor types
• Not all cholinergic receptors are identical
• Two types of cholinergic receptor - nicotinic and muscarinic
• Named after natural products showing receptor selectivity
Acetylcholine is natural messenger for both receptor types
Activates cholinergic
receptors at nerve synapses
and on skeletal muscle
Activates cholinergic
receptors on smooth
muscle and cardiac muscle
Nicotine
N
NMe
L-(+)-Muscarine
O
Me CH2NMe3
HO
P.E.S. Modern College of Pharmacy, Nigdi 24
25. • Nicotine comprises up the 3% the dry weight of the tobacco leaf
• When inhaled, it rapidly crosses the blood-brain barrier where it
activates (acts as an agonist at) the acetylcholine receptors
• Addiction to nicotine is reported to be one of the hardest
addictions to break.
P.E.S. Modern College of Pharmacy, Nigdi 25
26. • Muscarine is the active poisonous ingredient in several
species of mushrooms
• Ingestion causes severe nausea and diarrhea as the
muscarine acts as an acetylcholine agonist. Also causes
perspiration and lacrimation (tearing).
• The antidote is atropine, an acetycholine antagonist at the
muscarinic receptor. P.E.S. Modern College of Pharmacy, Nigdi 26
29. Cell
membrane
Five glycoprotein subunits
traversing cell membrane
Receptor
Binding
site Messenger
Control of Cationic Ion Channel:
4.1 Nicotinic receptor
Cell
membrane
Induced
fit
‘Gating’
(ion channel
opens)
P.E.S. Modern College of Pharmacy, Nigdi 29
30. The binding sites
a
a
g
d
b
Two ligand binding sites
mainly on a-subunits
Ion channel
2xa, b, g, d subunits
Binding
sites
4.1 Nicotinic receptor
Cell
membrane
a
ad
b
g
P.E.S. Modern College of Pharmacy, Nigdi 30
32. Activation of a signal protein
• Receptor binds messenger leading to an induced fit
• Opens a binding site for a signal protein (G-protein)
closed
messenger
induced
fit
open
Muscarinic receptor - G Protein coupled receptor
G-protein
bound
G-protein
splitP.E.S. Modern College of Pharmacy, Nigdi 32
33. Activation of membrane bound enzyme
• G-Protein is split and subunit activates a membrane bound enzyme
• Subunit binds to an allosteric binding site on enzyme
• Induced fit results in opening of an active site
• Intracellular reaction is catalysed
active site
(closed)
active site
(open)
Enzyme Enzyme
Intracellular
reaction
4.2 Muscarinic receptor - G Protein coupled receptor
subunit
P.E.S. Modern College of Pharmacy, Nigdi 33
34. 5. Cholinergic agonists
5.1 Acetylcholine as an agonist
Advantages
• Natural messenger
• Easily synthesised
Disadvantages
• Easily hydrolysed in stomach (acid catalysed hydrolysis)
• Easily hydrolysed in blood (esterases)
• No selectivity between receptor types
• No selectivity between different target organs
Ac2O
NMe3+
O HO NMe3 NMe3AcO
P.E.S. Modern College of Pharmacy, Nigdi 34
35. 5. Cholinergic agonists
5.2 Nicotine and muscarine as cholinergic agonists
Advantages
• More stable than Ach
• Selective for main cholinergic receptor types
• Selective for different organs
Disadvantages
• Activate receptors for other chemical messengers
• Side effects
P.E.S. Modern College of Pharmacy, Nigdi 35
36. 5. Cholinergic agonists
5.3 Requirements for cholinergic agonists
• Stability to stomach acids and esterases
• Selectivity for cholinergic receptors
• Selectivity between muscarinic and nicotinic receptors
• Knowledge of binding site
• SAR for acetylcholine
P.E.S. Modern College of Pharmacy, Nigdi 36
37. Acetoxy
Ethylene
bridge
4 o Nitrogen
Me O
NMe3
O
Acetoxy
Ethylene
bridge
Nitrogen
Me O
NMe3
O
6. SAR for acetlcholine
Quaternary nitrogen is essential
Bad for activity
O
CMe3
H3C
O
O
NMe2
H3C
O
P.E.S. Modern College of Pharmacy, Nigdi 37
38. • Distance from quaternary nitrogen to ester is important
• Ethylene bridge must be retained
6. SAR for acetylcholine
Bad for activity
O NMe3
H3C
O
OH3C
O
NMe3
Acetoxy
Ethylene
bridge
4 o Nitrogen
Me O
NMe3
O
Acetoxy
Ethylene
bridge
Nitrogen
Me O
NMe3
O
P.E.S. Modern College of Pharmacy, Nigdi 38
39. Ester is important
6. SAR for acetylcholine
Bad for activity
O
NMe3
H3C
NMe3
H3C
Acetoxy
Ethylene
bridge
4 o Nitrogen
Me O
NMe3
O
Acetoxy
Ethylene
bridge
Nitrogen
Me O
NMe3
O
P.E.S. Modern College of Pharmacy, Nigdi 39
40. Minimum of two methyl groups on quaternary nitrogen
6. SAR for acetylcholine
Bad for activity
O
N
H3C
O Et
Et
Et
Active
O
N
H3C
O Et
Me
Me
Acetoxy
Ethylene
bridge
4 o Nitrogen
Me O
NMe3
O
Acetoxy
Ethylene
bridge
4 o Nitrogen
Me O
NMe3
O
P.E.S. Modern College of Pharmacy, Nigdi 40
41. Methyl group of acetoxy group cannot be extended
6. SAR for acetylcholine
Bad for activity
O
NMe3
O
H3C
Acetoxy
Ethylene
bridge
4 o Nitrogen
Me O
NMe3
O
Acetoxy
Ethylene
bridge
Nitrogen
Me O
NMe3
O
P.E.S. Modern College of Pharmacy, Nigdi 41
42. Conclusions:
• Tight fit between Ach and binding site
• Methyl groups fit into small hydrophobic pockets
• Ester interacting by H-bonding
• Quaternary nitrogen interacting by ionic bonding
6. SAR for acetylcholine
Acetoxy
Ethylene
bridge
4 o Nitrogen
Me O
NMe3
O
P.E.S. Modern College of Pharmacy, Nigdi 42
43. SAR relationship have made it possible to MAP the receptor and prepare a
MODEL that can account for the affinity& the intrinsic activity of
cholinergic agonist.
Early attempts to map the cholinergic receptor showed the importance to
muscarinic potency of the Quat.amine and the Ester group separated by
2-C.
P.E.S. Modern College of Pharmacy, Nigdi 43
44. Esteratic
site
Anionic
site
Mapping of Muscarinic receptor
Fig. Original representation of the Muscarinic receptor.
+
_
+
NO
O
CH3
CH2 CH2
CH3 CH3
CH3
C
Ester grouping Alkyl amine chain Cationic head
P.E.S. Modern College of Pharmacy, Nigdi 44
47. • Possible induced dipole dipole interaction between quaternary nitrogen and
hydrophobic aromatic rings in binding site
• N+ induces dipole in aromatic rings
7. Binding site (muscarinic)
R
NMe3
d -
d -
d +d +
P.E.S. Modern College of Pharmacy, Nigdi 47
48. O
C
H
H
OMe
H
H
Me
N
Me
Me
• Several freely rotatable single bonds
• Large number of possible conformations
• Active conformation does not necessarily equal the most stable conformation
8. Active conformation of acetylcholine
P.E.S. Modern College of Pharmacy, Nigdi 48
49. Conformation of Ach:-
Because of free rotation around most covalent bonds, Ach and its analogs can
exist in many favorable conformations.
The two structures below represents extremes in possible conformations.
N
+
O
CH3
O
CH3
CH3
CH3
N
+
OCH3
O
CH3
CH3
CH3
Quasi-ring conformation Extended conformation
P.E.S. Modern College of Pharmacy, Nigdi 49
50. This conformations are illustrated by Newman projection as
N(CH 3)3 N(CH 3)3
OCOCH 3
OCOCH 3
H
H
H
H
H
H
H
H
synclinal (gauche or skew ) Antiperiplanal (anti or transoid)
P.E.S. Modern College of Pharmacy, Nigdi 50
52. MUSCARINE
O
Me CH2NMe3
HO
CH2NMe3Me
O
O
O
O
Me
NMe3
H
H
Rigid Analogues of acetylcholine
• Rotatable bonds ‘locked’ within ring
• Restricts number of possible conformations
• Defines separation of ester and N
8. Active conformation of acetylcholine
Muscarinic
receptor
O
N
4.4A
Nicotinic
receptor
O
N
5.9A
P.E.S. Modern College of Pharmacy, Nigdi 52
53. • Neighbouring group participation
• Increases electrophilicity of carbonyl group
• Increases sensitivity to nucleophiles
9. Instability of acetylcholine
O
C
O
Me3N
H3C
d
d
P.E.S. Modern College of Pharmacy, Nigdi 53
54. 10. Design of cholinergic agonists
Requirements
• Correct size
• Correct pharmacophore - ester and quaternary nitrogen
• Increased stability to acid and esterases
• Increased selectivity
P.E.S. Modern College of Pharmacy, Nigdi 54
55. Use of steric shields
Rationale
• Shields protect ester from nucleophiles and enzymes
• Shield size is important
• Must be large enough to hinder hydrolysis
• Must be small enough to fit binding site
10. Design of cholinergic agonists
P.E.S. Modern College of Pharmacy, Nigdi 55
56. CHOLINOMIMETICS OR CHOLINERGIC AGONISTS
Have their primary action the excitation or inhibition of autonomic
effector cells that are Innervated by postganglionic parasympathetic
nerves.
They differ from acetylcholine In,
• Their selectivity on muscarinic and nicotinic receptors.
• Their chemical stability.
• Their resistance to hydrolysis by cholinesterase and
• Their duration of action.
On the structural basis, the cholinomimetic agents can be divided into,
Acetylcholine and several synthetic choline esters.
Naturally occurring and synthetic alkaloids.
Cholinesterase inhibitors or anticholinesterases and
Ganglionic stimulants.
• The last two categories do not act at postganglionic cholinergic
effector sites and produce their effects by acting In an Indirect way.
P.E.S. Modern College of Pharmacy, Nigdi 56
57. Structure-Activity Relationship
Modifications of the onium (Quatarnary ammonium) group :
• The trimethylammonium group is the optimal functional requirement
for activity, although following are the exceptions.
• Phosphonlum, sulphonium, arsenonium or substances larger than
methyl on the nitrogen, had less activity and not used clinically.
P.E.S. Modern College of Pharmacy, Nigdi 57
58. SAR
Modifications of the Ethylene Bridge :
• In studying a series of n-alkyl tri-methyl ammonium salts, Ing’s five atom
rule : for maximal muscarinic activity, there should be not more than four
atoms between the nitrogen and terminal carbon atom.
• Replacement of the H-atoms of the ethylene bridge by alkyl groups
produces far less active compounds except when a single, methyl group Is
placed either at a or P to the quaternary nitrogen atom.
• The presence of a methyl group β to the quaternary nitrogen atom
increases the muscarinic activity, e.g. Methacholine.
• The high selective muscarinic action is due to orientation of methyl group of
methacholine In the same position as a methylene group in muscarine.
• Moreover the added methyl group hinders the attack of esterase enzyme,
thus slows down enzymatic hydrolysis.
• A methyl group alpha to the nitrogen increases nicotinic activity e.g. Acetyl
Methyl- choline.
P.E.S. Modern College of Pharmacy, Nigdi 58
59. SAR
Modifications of the Acyl Group :
• When the acyl group is substituted by its higher homologues (i.e. the
propionyl, butyryl etc.), less active compounds are formed.
• Choline esters of aromatic or higher molecular weight acids are cholinergic
antagonists rather than agonists.
• When the terminal methyl group Is replaced by -NH2 group, the resulting
compound, (the carbamic acid ester), however, is a potent cholinergic agent
with both muscarinic and nicotinic activities.
Carbachol is certainly stable to hydrolysis and has the right size to fit the
cholinergic receptor. The carbamic acid ester of (3-methylchollne Is also a
stable therapeutic agent. The measured Inter- prosthetic distances In
acetylcholine are 7.0 A ketone oxygen to methyl and 5.3 A ether oxygen to
methyl. Obviously, the interprosthetlc distances for acetylcholine,
methacholine, carbaminoylchollne. and urechollne are the same.
Apparently, if the interprosthetic distances are optimal, the receptors on
the cell do not differentiate between ether, ketone, ester, or acetyl oxygen
atoms.
P.E.S. Modern College of Pharmacy, Nigdi 59
60. SAR
• In carbachol, the terminal methyl group of acetylcholine is
replaced by -NH2 group, while size of the molecule remains
the same as that of acetylcholine. So It becomes apparent
that the size of the molecule may be more Important to Its
activity than the acyl group present. Similarly, the ether
oxygen appears to be of primary Importance for high
muscarinic activity. As a result of such reasoning, ethers of
choline and alkylamino- ketones were examined for activity.
• The reduced biological activity of compounds In which
oxygen is replaced by sulphur (e.g. thiomuscarine) suggests
the presence of H-bonding or dipole-dipole interaction
between the drug and the receptor because sulphur atom
has a less ability to form H-bonds with the receptors.P.E.S. Modern College of Pharmacy, Nigdi 60
61. SAR
• The concept that the ester i.e. carbonyl or other
group Is not essential for activity but may enhance It
by Increasing the affinity of the molecule for the
receptor was confirmed by a study of the muscarinic
properties of N-alkyltrimethyl ammonium salts.
• Compounds In this series showed muscarinic activity
when n - 1, 2, 3 or 4. Compounds with groups larger
than pentyl were partial agonists and those with
groups larger than heptyl were antagonists. This
appears to believe the hypothesis that size rather
than functional groups Is necessary for the Intrinsic
activity.
P.E.S. Modern College of Pharmacy, Nigdi 61
62. Classic SAR
The classic SAR for muscarinic agonist activity can be
summarized as follows:
• The molecule must possess a nitrogen atom capable of
bearing a positive charge, preferably a quaternary
ammonium salt.
• For maximum potency, the size of the alkyl groups
substituted on the nitrogen should not exceed the size
of a methyl group.
• The molecule should have an oxygen atom, preferably
an ester-like oxygen, capable of participating in a
hydrogen bond.
• There should be a two-carbon unit between the oxygen
atom and the nitrogen atom.
P.E.S. Modern College of Pharmacy, Nigdi 62
63. ADVERSE REACTIONS
• All synthetic choline esters should never be
administered by Intravenous route.
• They are usually administered preferably by
oral or by subcutaneous route.
• The usual side-effects Include, salivation,
vomiting and severe gastrointestinal cramps.
CONTRAINDICATIONS
• These synthetic derivatives of acetylcholine
are contraindicated In patients suffering from
peptic ulcer, bronchial asthma, hypotension,
presence of urinary tract or gastrointestinal
obstruction.
P.E.S. Modern College of Pharmacy, Nigdi 63
64. 10. Design of cholinergic agonists
Methacholine
Properties
• Three times more stable than acetylcholine
• selective muscarinic agonist with very little activity at nicotinic receptors
• Increasing the shield size increases stability but decreases
activity
• Selective for muscarinic receptors over nicotinic receptors
• S-enantiomer is 240 folds more active/ potent than the R-enantiomer
• Stereochemistry matches muscarine
• Not used clinically
• sed via inhalation for the diagnosis of asthma
asymmetric centre
hinders binding to esterases
and provides a shield to
nucleophilic attack
MUSCARINE
O
Me CH2NMe3
HO
H
CH2NMe3Me
Me
O
O
(S) (R)
Me
O
O
H
Me CH2NMe3
Me O
NMe3
O Me
*
(2-hydroxypropyl)trimethylammonium chloride acetate
P.E.S. Modern College of Pharmacy, Nigdi 64
65. • The primary clinical use of methacholine is as an
acetylcholine agonist at the muscarinic receptor
• As such, it is utilized in a test for asthma, called the
‘bronchial challenge test’
• The methacholine provokes bronchoconstriction
• Asthmatic patients, which already have airway hyperactivity,
are more sensitive to the effect of methacholine, and this
reaction can be quantified using a breathing test called
spirometry.. P.E.S. Modern College of Pharmacy, Nigdi 65
66. 10. Design of cholinergic agonists
Use of electronic factors
• Replace ester with urethane
• Stabilises the carbonyl group
H2N
C
O
C
O
H2N
d
H2N
C
O
d
=
The carbamyl group of carbachol decreases the electrophilicity of the carbonyl and,
thus, can form resonance structures more easily than ACh can
P.E.S. Modern College of Pharmacy, Nigdi 66
67. 10. Design of cholinergic agonists
Properties
• shows no selectivity for muscarinic or nicotinic receptors. Because it is a
carbamate ester, Resistant toward acid-, base-, or enzyme (AChE)-catalyzed
hydrolysis than acetylcholine.
• exhibit weak anticholinesterase activity
• Long lasting
• NH2 and CH3 are equal sizes. Both fit the hydrophobic pocket
• NH2 = bio-isostere
• Muscarinic activity = nicotinic activity
• Used topically for glaucoma
Carbachol
O
C
O
H2N
NMe3
P.E.S. Modern College of Pharmacy, Nigdi 67
68. • Glaucoma is an eye disease, characterized by increased
intraocular pressure. It leads to irreversible loss of vision and is
the second leading cause of blindness.
• Treatments for glaucoma focus on relieving the pressure.
• Carbachol causes miosis (constriction of the pupil), by
contracting the ciliary muscle, tightening the trabecular meshwork
and allowing increased outflow of the aqueous humourP.E.S. Modern College of Pharmacy, Nigdi 68
69. 10. Design of cholinergic agonists
Steric + Electronic factors
Properties
• nonspecific in its action on muscarinic receptor subtypes but appears to be more
effective at eliciting pharmacological action of M3 receptors
• Very stable
• Orally active
• Used in relief of urinary retention and abdominal distention after surgery
• cholinergic crisis if it is given by intravenous or intramuscular injection
Bethanechol
*H2N
C
O
O
NMe3
Me
(2-hydroxypropyl)trimethylammonium chloride carbamate
Cl-
P.E.S. Modern College of Pharmacy, Nigdi 69
70. Pilocarpine Hydrochloride
• Hydrochloride of an alkaloid obtained from the dried
leaflets of Pilocarpus jaborandi or P. microphyllus.
• nonselective agonist on the muscarinic M3 receptors
in smooth muscle to cause contractions in the gut,
trachea and eye.
• treatment of glaucoma
• treatment of xerostomia (dryness of the mouth)
caused by radiation therapy of the head and neck,
Sjogren’s syndrome. or as a side effect of some
psychotropic drugs.P.E.S. Modern College of Pharmacy, Nigdi 70
71. Cevimeline Hydrochloride
• Nonclassical muscarinic agent
• Quinuclidine derivative exhibit partial direct M1
agonistic activity in CNS and affinity for M3
receptor in epithelial tissue of lacrimal and
salivary glands.
• Available as oral capsule
• Treat xerostomia
Evoxac
2-Methyspiro(1,3-oxathiolane-5,3)quinuclidine
P.E.S. Modern College of Pharmacy, Nigdi 71
72. Future Muscarinic Agents
• Focus on discovering the agents used to treat
Alzheimer and other cognitive disorders.
P.E.S. Modern College of Pharmacy, Nigdi 72
73. Cholinergic Agonists
Oxotremorine:
[1-(-pyrrolidono)-4-pyrrolidino-2-butyne.
CNS muscarinic stimulant.
Its action on the brain produces tremors in experimental animals.
It increases ACh brain levels in rats up to 40% and has been studied as a drug in
the treatment of Alzheimer's disease.
Oxotremorine, as a cholinergic agonist. facilitates memory storage. These findings
have served as important leads in the development of agents useful in treating
Alzheimer's disease.
it possesses groups that do not occur in other highly active muscarinic agents,
oxotremorine’s trans conformation shows that distances between possible active
centers correspond with ()-
Muscarine.
P.E.S. Modern College of Pharmacy, Nigdi 73
74. Arecoline. Arecoline is an alkaloid obtained from the seeds of the
betel nut (Areca catechu). For many years, natives of the East
Indies have consumed the betel nut as a source of a euphoria-
creating substance.
Xanomeline:
In clinical trials
Nonclassical bioisoster of ester moiety of Arecholine.
M1 M4 agonist
Orally not tolarated, transdermal effective.
P.E.S. Modern College of Pharmacy, Nigdi 74
75. 10. Design of cholinergic agonists
Nicotinic selective agonist
Me
C
O
O * asymmetric centre
NMe3
Me
*
P.E.S. Modern College of Pharmacy, Nigdi 75
76. 11. Uses of cholinergic agonists
Nicotinic selective agonists
Treatment of myasthenia gravis
- lack of acetylcholine at skeletal muscle causing weakness
Muscarinic selective agonists
• Treatment of glaucoma
• Switching on GIT and urinary tract after surgery
• Treatment of certain heart defects. Decreases heart muscle activity and
decreases heart rate
P.E.S. Modern College of Pharmacy, Nigdi 76