Introduction parasympathetic nervous system cholinergic drugs Anticholinergic agents Divisions of Autonomous nervous system Drugs acting on adrenergic nervous system Adrenergic agents

1. ADVANCED MEDICINAL CHEMISTRY
-Mr. Akshay Ramchandra Yadav
( M.pharm 1st year)
Pharmaceutical chemistry Dept.
Rajarambapu College of Pharmacy,
Kasegaon
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2.  The autonomic nervous system is a control system that acts largely
unconsciously and regulates body functions such as the heart rate, digestion,
respiratory rate, pupillary response, urination.
 The ANS is part of the peripheral nervous system and it also controls some of
the muscles within the body. We are often unaware of the ANS because it
functions involuntary and reflexively.
For example, we do not notice when blood vessels change size or when our
heart beats faster.
AUTONOMIC NERVOUS SYSTEM
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3. 1.SYMPATHETIC NERVOUS SYSTEM:
The sympathetic nervous system primary process is to
stimulate the body's fight-or-flight response.
For example-the sympathetic nervous system can accelerate
heart rate, widen bronchial passages, decrease motility of the
large intestine, constrict blood vessels, increase peristalsis in
the esophagus, cause pupillary dilation.
2. PARASYMPATHETIC NERVOUS SYSTEM:
The parasympathetic nervous system is one of three divisions
of the autonomic nervous system. Sometimes called the rest
and digest system, the parasympathetic system conserves
energy as it slows the heart rate, increases intestinal and gland
activity.
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5. Acetyl choline (Ach) is neurotransmitter which porpagates impulse transmission
in parasympathetic division.
Ach also function as a neurotransmitters.
 Ach causes contraction of smooth muscles, cardiac inhibition in man or laboratory
animals.
 Parasympathetic nerve fibers liberates acetylcholine hence this system is also called
cholinergic nervous system.
 Ach is biosynthesized by acetylation of choline molecule in nerve terminals.
 The free acetylation present in blood and other tissues, get quickly hydrolysed by
cholinesterase enzyme into acetic acid and choline as shown below:-
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6. ACTION OF ACETYLCHOLINE-
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8. 1.CHOLINERGIC AGONIST-
a. Choline esters
 Acetylcholine
SAR-
1. Any change in the ethylene bridge may affect the chemical stability of Ach
molecule.
2. A quaternery ammonium group is essential for manifestation of both
muscarinic and nicotinic receptors.
3. If one or more methyl group is present on nitrogen atom are replaced by
hydrogen or ethyl group then both the activities i.e muscarinic and nicotinic
activity is reduced.
4. Quaternary nitrogen atom may be replaced by Arsenic, antimony ,
phosphorous or sulphur atom without the loss of Ach like activities. 8

9. Bethanicol-
 Mode of action-
a) It has more selective muscarinic action on GIT and urinary bladder.
b) It increases tone of contraction of intestine
C) It causes emptying of urinary bladder due to contraction of muscle of bladder and
relaxation of sphincter muscle.
 Use-
It is used to get relief from abdominal distension (stress) after surgery.
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10. 2. ANTICHOLINETERASE
These enzymes causes inhibition of cholinesterase enzyme which is responsible for
hydrolysis of acetylcholine into acetic acid and choline.
a. Reversible anticholinesterase
- They having structural similarities with Ach hence they are combined with anionic and esteric
sites.
-They having a great affinity towards active sites but no intrensic activity.
example- i. Physostigmine
SAR-
1.The distance between other oxygen & nitrogen
appproximately same as that of distance between
other oxygen and nitrogen present in Ach.
2.Two heterocyclic rings are not essential for
anticholinesterase activity during hydrolysis the
phenolic fragment of these drug is eliminated ,
leaving the carbonyl group attach to the enzyme.
Use- To treat glaucoma
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11. ii.Neostigmine
 SAR-
1.In neostigmine stability is increased due to hydrolysis by using dimethyl
carbamte in place of methyl carbamate group.
2.Because of charged nitrogen neostigmine cannot crosses blood brain barrier and
do not causes CNS related side effects.
 Use-
1.It is used in treatment of mysthenia gravis.
2.It is used as an antidote to non-depolarizing neuromuscular blocking drugs.
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12. b. Irreversible Anti cholinesterase
Irreversible anticholinesterase causes inhibition of anticholinesterase
irreversibly.
e.g- methyl parathion
 MOA-
I. Parathion is a organophosphorous compound.
ii. It inhibits cholinesterase enzyme .
 Use-
i. It is used to treat glaucoma.
ii. It is used to treat mysthenia gravis.
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13. Dicyclomine
MOA-
These class of drugs that block neurotransmitter Ach in PNS.
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15. 1. Cationic group-
i. N-atom must be tertiary amine which undergo quaternisation at physiological Ph.
ii.Highly alkyl group on nitrogen causes stearic hinderance.
iii.Quaternisation increases anticholinergic action and decreases cholinergic action.
2.Hydroxyl group-
i.It is important for affinity and in presence of –OH more active compound.
e.g amino alcohol ester.
ii.In amino alcohol ester ,hydroxyl group contain carboxylic acid which having maximum activity.
e. Atropine.
SAR OF ANTICHOLINERGIC DRUGS-
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16. 3.Cyclic substituents-
i. At least one cyclic substituents is a common feature in
anticholinergics.
ii. Introduction of large cyclic group decreases activity.
Adverse effects-
 Tachycardia.
 Blurred vision.
 Dry mouth and skin.
Use-
 It is used to treat parkinsonism disease.
 Atropine is specific antidote for mushroom poisioning.
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17. These are the drugs which produces action similar to that of action produced by
adrenaline or causes sympathetic stimulants.
Adrenaline and nor- adrenaline are the two transmitters-
 Relaxation of smooth muscles.
 Increases in heart activity/ tachycardia.
 Decreases the gland secreation.
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18. CLASSIFICATION OF ADRENERGIC DRUGS OR
SYMPATHOMIMETIC DRUGS-
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19. I. DIRECTLY ACTING DRUGS
1. Non-selective beta 1 & Beta 2 blockers.
example- propranolol
Propranolol belongs to the group of beta blocking agents known as
acyclopropanolol amine (-OCH2) Group has been incorporated into molecule
between aromatic ring and ehtylamine side chain.
MOA-
It blocks the action of epinephrine and nor-epinephrine on both beta 1 and beta 2
adrenergic receptor.
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20. SAR-
i. Nature of aromatic ring and its substituents
are primary determinants of beta antagonist
activity.
ii. Propranolol has high lipid solubility which
allows it to penetrate nerve tissue and
shows cardiodepressant effect in addition to
its beta blocking activity, to avoid this
problem use of polar group like methane
sulphonamide.
iii. Alkyl on ortho group position on phenyl
ring provides good activity.
e.g-
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21. 2. MIXED ACTING DRUGS-
 SAR-
Substitution of amine group R3 i.e CH3 Increased selectivity.
Substitution if alpha carbon blocks metabolism by MAO.
OH at beta carbon enhances adrenoreceptor properties.
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22. They block the release action of catecholamines (epinephrine,
norepinephrine, dopamine), which are released in response to stress.
Centrally acting antiadrenergic agents make the heart beat slower and with
less force, and relax the blood vessels.
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23. 1st y
m
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24. A. ADRENERGIC RECEPTOR ANTAGONIST-
Prazosin:
(i) Prazosin is a selective blocker of postsynaptic α1 receptors, producing
vasodilation of both arteries and veins.
(ii) Prazosin reduces peripheral vascular resistance and lowers arterial blood
pressure.
SAR-
a. Amine group present in structure is essential for the
activity.
b. If five membered ring in structure is removed then activity
decreases.
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25. 2.DRUGS INHIBITING NE SYNTHESIS-
SAR-
a. Methyl group is replaced with other group than activity decreases.
b. Hydroxy group attached with ring structure shows activity.
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26. 3.DRUGS INHIBITING NE STORAGE-
e.g- Reserpine
 SAR-
 If methoxy group is removed then sympatholytic activity decreases.
 Nitrogen atom present in structure is essential for activity.
 Amine group present in structure shows antiadrenergic activity.
 MOA-
Stimulate NE secreation and inhibit sympathetic activity and reduces BP.
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