Antcholinergic Drugs

Presented By:
Mr. Kiran D. Baviskar,
Assist. Professor
Dept. of Pharmaceutics,

Smt. Sharadchandrika Suresh Patil College of Pharmacy, Chopda.

SAR of Anticholinergics:

R1
R2---------X –(CH2)n-N
R3
1.Substituents R1, & R2 should be carbocyclic or heterocyclic
rings for maximal potency.
The rings can be identical but the more potent compounds
have different rings.
Generally, one ring is aromatic & other saturated or possessing
only one olefinic bond.

Substituents Rl ,& R2 can be combined into a fused aromatic

tricyclic ring system such as that found in propantheline.
The size of these substituents is limited e.g. Substitution of
naphthalene rings for Rl & R2 affords compounds that are
inactive, because of steric hindrance of the binding of these
compounds to muscarinic receptor.
2. The R3 substituent can be a hydrogen atom, a
hydroxyl group, a hydroxymethyl group, a
carboxamide or it can be a component of one of the
R1, & R2 ring system.

When this substituent is either a hydroxyl or a

hydroxymethyl group, the antagonist is usually more
potent than the same compound without this group.

The hydroxyl group increases binding strength by

participating in a hydrogen bond interaction at the
receptor.
3. The X- substituent is an ester in most potent
anticholinergics but it is not an absolute necessity for
muscarinic antagonist activity. This substituent can be
ether oxygen or it can be absent completely.

4. The N substituent is a quaternary ammonium salt in

potent anticholinergic drugs but tertiary amine also
possesses antagonist activity by binding to receptor in
the cationic site. The alkyl substitutes are usually
methyl, ethyl, propyl or isopropyl.
5.The distance between the ring substituted carbon &
the amine nitrogen is not critical, the length of the
alkyl chain connecting these may be from 2 to 4
carbons.
Most potent anticholinergic agents have 2 methylene
units in this chain.
THERAPEUTIC APPLICATIONS
1. Muscarinic antagonists are employed as both prescription
drugs & OTC medications.
Because they act as competitive (reversible) antagonist of
Acetylcholine. These compounds have pharmacological
effects opposite to that of muscarinic agonist.
Responses of Muscarinic antagonist include decreased
contractions of smooth muscle of the GI tract & urinary tract,
dilation of pupils & decreased gastric, mucociliary & salivary
secretions.
So anticholinergic compounds have therapeutic value in
treating smooth muscle spasm associated with increased
tone of the GIT or with overactive bladder, in
ophthalmologic examinations & in treatment of gastric
ulcers.
2. Compounds possessing muscarinic antagonist activity are
the common components of cold & flu remedies that act to
reduce nasal & upper respiratory tract secretions.

3. Anticholinergic agent decrease gastric acids secretion &

were widely used to manage peptic ulcers. When used
systemically, they produce side effects such as blurred vision,
photophobia, dry mouth and difficulty in urination. These side
effects reduce patient compliance.
4. Anticholinergic agent exhibit mydriatic action and can be
used with caution because of their effect on intraocular
pressure. Drainage of canal of schlemm is restricted by the iris
when pupil is dilated and this cause an increase in intraocular
pressure. Hence these are contraindicated in patients with
glaucoma.

5. Atropine is used in treatment of central & peripheral

symptoms associated with poisoning by organophosphorous
anticholinesterase agents.
1. Solanaceous alkaloids and its synthetic analogues
e.g. Atropine, Hyoscyamine, Hyoscine (scopolamine),
Homatropine, Tiotropium, Ipratropium.

2. Amino alcohol esters

e.g. Propantheline, Methantheline, Oxybutynin, Dicyclomine,
Cyclopentolate, Clidinium, Eucatropine, Glycopyrrolate.

3. Amino alcohol ethers

e.g.Benztropine,Orphenadrine.
4. Amino alcohols
e. g. Biperiden, Procyclidine, Tridihexethyl chloride,
trihexphenidyl, Tolterodine.

5. Amino amides
e.g. Tropicamide, Isopropamide, Darifenacin.

6. Miscellaneous ions
e.g. Diphemanil, Ethopropazine, Papaverine.