e-content of Adrenergic and cholinergic agents for M.pharm students

1. Presenting by,
Mr. PURUSHOTHAM K N
Assistant Professor
Department of Ph. Chemistry
SACCP
B. G. Nagar
2021-2022
ADRENERGIC & CHOLINERGIC AGENTS

2. Introduction
AUTONOMIC NERVOUS SYSTEM
 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.

3. Divisions OF Autonomous Nervous System
I.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, 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

5. PARASYMPATÄOC NERVOUS SYSTEM
Acetyl choline (Ach) is neurotransmitter which propagates 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:-

6. Action Of Acetyl Choline

8. CHOLINERGIC AGONIST
Choline esters
Acetyl Choline
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 Le 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.

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.

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.
- To treat glaucoma

11. Irreversible Anti cholinesterase
Irreversible anticholinesterase causes inhibition of anticholinesterase irreversible.
Eg:- methyl parathion
MOA-
Parathion is a organophosphorous compound.
It inhibits cholinesterase enzyme.
Use
It is used to treat glaucoma.
It is used to treat myasthenia gravis.

12. Irreversible Anti cholinesterase
Irreversible anticholinesterase causes inhibition of anticholinesterase irreversibly.
Eg : methyl partition
MOA-
Parathion is a organophosphorous compound.
It inhibits cholinesterase enzyme.
Use
It is used to treat glaucoma.
It is used to treat myasthenia gravis.

14. MOA of Anticholinergic Drugs

15. Cation group
N-atom must be tertiary amine which undergo quaternisation at physiological Ph.
Highly alkyl group on nitrogen causes stearic hinderance.
Quaternisation increases anticholinergic action and decreases cholinergic action.
Hydroxyl group
It is important for affinity and in presence of –OH more active compound.
Eg: amino alcohol ester
In amino alcohol ester , hydroxyl group contain carboixylic acid which having maximum activity.
e. Atropine.

16. Cyclic substitution
At least one cyclic substituent is a common feature in
anticholinergics.
Introduction of large cyclic group decrease 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

17. Drugs Acting on Adrenergic Nervous System
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.
Increase in heart activity.
Decrease the gland secreation.

18. Classification of Adrenergic Drugs OR Sympathomimetic Drugs.

19. Directly Acting Drugs
1. Non-selective beta 1 & beta 2 blockers.
example- propranolol
Propranolol belongs to the group of beta
blocking agents known as acyclopropranol
amine Group has been incorporated into
molecule between aromatic ring and
ethylamine side chain.
MOA-
It blocks the action of epinephrine and nor-
epinephrine on the both beta1 and beta 2
adrenergic receptor.

20. Nature of aromatic ring and its substituents are primary determinant of beta
antagonist activity. Propranolol has high lipid solubility which allows it to
penetrate nerve tissue and shows cardiodepressant effect in addition to
propranolol 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.

21. SAR-
Substutional of amino group R3 i.e CH3 Increased selectivity
Substitution if alpha carbon blocks metabolism by MOA.
OH at beta carbon enhances adrenoreceptor properties

22. SYMPATHOLYTIC OR ANTIADRENERGIC AGENTS
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.

24. Prazosin
(i) Prazosin is a selective blocker of postsynaptic al receptors, producing
vasodilation Of both arteries and veins.
Prazosin reduces peripheral vascular resistance and lowers arterial blood pressure.
SAR-
a. Amino group present in the structure is essential for the activity.
b. If five membered ring in structure is removed then activity decreases.

25. Centrally acting sympatholytics
Methyldopa
Mechanism of action
Methyldopa is an α2 adrenergic receptor agonist acts centrally by decreasing the sympathetic outflow
which in turn lowers B.P.
SAR
If methoxy group is removed then sympatholytic activity decreases.
Nitrogen atom present in structure is essential for the activity.
Amine group present in structure shows antiadrenergic activity.

26. Drugs Inhibiting NE Storage
Stimulate NE secreation and inhibit sympathetic activity and reduces BP.
SAR-
If methoxy group is removed than sympatholytic activity decreases.
Nitrogen atom present in structure is essential for activity.
Amine group present in structure shows adrenergic activity.
MOA

27. THANK YOU