Anticholinergic agent defination, classification, SAR, structure, etc

1. Cholinergic
Antagonist
Presented by
- Ashok Gautam
Skb college of pharmacy

2. Cholinergic antagonist
• These drugs block the response of Ach in the
muscarine receptor by competitively binding to
it and inhibiting any response.
• They have opposite pharmacological
response of Ach

3. SAR
• The R1 or R2 groups must be carbocyclic or heterocyclic
• The R3 group can be hydrogen, hydroxyl (-OH),
hydroxymethyl (-CH2OH), amide
• The X is mostly Ester in most potent derivatives but it can
be a ether oxygen or absent completely
• The N substituent cab be both quaternary ammonium salt
or tertiary amine with different alkyl groups
• The distance between the ring substituted carbon and
nitrogen is not fixed but maximum potency requires about
2 carbon units
• (Note: The SAR does not say anything about selectivity for
muscarinic subtypes)
C X (CH2) N substituent
R1
R3
R2
General framework of Anticholinergics

4. • Medical use
In Sooth muscle spasm
In cold n flu (to reduce nasal secretion)
Previously in ulcer (but now replaced by H2
antagonist and proton inhibitors)
Overactive bladder (to much urination)
Motion sickness
Treat organophosphate poisoning
Parkinson (brain disease where nerves start
degrading and person slowly goes crazy)

5. SAR of Cholinergic Agent v/s and
Anticholinergic Agent
A) Nitrogen group
• In agonist the N can only be
quanternary but
• In antagonist N can be both
quanternary or tertiary
Methacholone Orphendrine

6. B) Ethylene group
• In agonist the no of ethylene is fixed at
only 2 but
• In antagonist no of ethylene can range
from 2-4
Bethaneco
l
carbamat
e
Glycopyrrolate

7. C) Selectivity
• In agonist the methyl substitution in
ethylene group controls selectivity of
muscarinic or nicotinic but
• In antagonist no such feature is
present. Still It only antagonizes
muscarinic only
Methacholone
Muscarinic selective

8. Classification
A)Solanaceous alkaloid and analogs
• Atropine
• Hyoscyamine
• Scoplamine
• Homatropine
• Ipratropium and Tiotropium
B) Synthetic Cholinergic blocking agent
1) Aminoalcohol Esters
• Clinidium bromide
• Cyclopentolate
• Dicyclamine
• Glycopyrrolate
• Mepenzolate
• Methantheline
• Oxyphencyclimine
• Propantheline
• Oxybutynin
• Solifenacin

9. 2) Aminoalcohol Ethers
• Benztropine
• Orphenadrin
3) Aminoalcohol
• Biperiden
• Procyclidine
• Trihexethyl chloride
• Tolterodine
3) Aminamides
• Isopropamide
• Tropicamide
• Darifenacin
4) Miscellaneous
• Diphemanil
• Ethopropazine
• Papaverine

10. Atropine
Atropine
• Anticholinergic, blocks muscarinic receptors
• Alkaloid extracted from Solanaceae plant
• first anticholinergic.
• It is an Ester of tropine and tropic acid and used as a sulphate Salt in
racemic from
• At therapeutic does it can penetrate the brain and stimulate the CNS
• Uses
• Treat Bardycardia
• Reduce secretion before surgery
• Treat Iritis (painful inflammation of eye)
• Organophosphate poisoning (only to decrease muscarinic action, not an
antidote like PAM)
• MOA – It competitively binds to muscarinic receptor and antagonizes it
thus blocking all cholinergic effects

11. Hyoscyamine
Hyoscyamine
• It is the levorotary isomer of atropine
USE:
• various gastrointestinal disorders including spasms, peptic ulcers,
irritable bowel syndrome, pancreatitis, and cystitis.
• Used to relieve some heart problems,
• control some of the symptoms of Parkinson's disease,
• control of respiratory symptoms

12. Scopolamine
Scopolamine
• In the form of a levorotatory
• Action on the higher nerve centers
• Transdermal patch of scopolamine is available
side effects:
• include sleepiness, blurred vision, dilated pupils, and dry mouth
Use:
Postoperative nausea and vomiting and sea sickness, Motion sickness (where it
is often applied as a transdermal patch behind the ear), Gastrointestinal spasms,
Renal or biliary spasms, Aid in radiology and endoscopy, Irritable bowel
syndrome, Clozapine-induced hypersalivation, Eye inflammation

13. Ipratropium bromide
Ipratropium
• It is a Quaternary ammonium derivative of atropine
• used in inhalation therapy to produce dilation of bronchial smooth
muscle for acute asthmatic attacks.
• The drug produces bronchodilation by competitive inhibition of
cholinergic receptors bound to smooth muscle of the bronchioles

14. Tiotropium bromide
Tiotropium bromide
• Used in an inhalation device to deliver the drug into the lungs.
• It is indicated in the treatment of chronic obstructive pulmonary
disease (COPD), including chronic bronchitis and emphysema
• Long-acting, 24-hour

15. 1) Aminoalcohol
Esters
Clinidium bromide
Clinidium bromide
• Marketed alone and in combination with the minor tranquilizer
chlordiazepoxide (Librium) in a product known as Librax.
• For the treatment of GI complaints is the use of an anxiety-reducing
agent together with an anticholinergic agent

16. Cyclopentolate
Cyclopentolate
• It is used only for its effects on the eye,
• Acts as a parasympatholytic.
• When placed in the eye, it quickly produces cycloplegia and mydriasis.
• Usefulness in refraction studies.
• Can be used, as a mydriatic in the management of iritis, iridocyclitis,
keratitis

17. Dicyclamine
Dicyclamine
• Used for its spasmolytic effect on various smooth muscle spasms,
particularly those associated with the GI tract.
• It is also useful in dysmenorrhea, pylorospasm, and biliary
dysfunction.

18. Glycopyrrolate Mepenzolate
Methantheline Oxyphencyclimine

19. 2) Aminoalcohol
Ethers
Benztropine
• Has anticholinergic, antihistaminic, and local anesthetic
properties.
• Its anticholinergic effect makes it applicable as an antiparkinson
agent.
• It is about as potent anticholinergic as atropine

20. Orphenadrin
Orphenadrin
• Closely related to diphenhydramine structurally but has much lower
antihistaminic activity and much higher anticholinergic action
• It does reduce voluntary muscle spasm, however, by a central inhibitory
action on cerebral motor areas.

21. 3) Aminoalcohol
Biperiden
Biperiden
• Has a relatively weak visceral anticholinergic,
but a strong nicotinolytic action in terms of its
ability to block nicotine induced convulsions
• Has a relatively strong musculotropic action,
which is about equal to that of papaverine, in
comparison with most synthetic anticholinergic
drugs

22. Procyclidine
Procyclidine
• Effective peripheral anticholinergic
• Ability to relieve voluntary muscle spasticity by its central action
• Treatment of Parkinson syndrome
• Reduce muscle rigidity in postencephalitic, arteriosclerotic, and idiopathic types
of the disease

23. 4) Aminoamides
Isopropamide
Isopropamide
• Potent anticholinergic,
• Producing atropine-like effects peripherally
• Long duration of action.
• A single dose can provide antispasmodic and antisecretory effects for as
long as 12 hours.
USE:-
• It is used as adjunctive therapy in the treatment of peptic ulcer and other
conditions of the GI tract associated with hypermotility and
hyperacidity.

24. Tropicamide
Tropicamide
• Effective anticholinergic for ophthalmic use
• Produces short acting mydriasis and cycloplegia
• To achieve mydriasis, either 0.5% or 1.0% concentration may be used
• Treatment of acute iritis, iridocyclitis, and keratitis

25. 5) Miscellaneous
Diphemanil
Ethopropazine
Papaverine