Subject: Pharmaceutical Chemistry

Unit 6.2: CHOLINERGIC AND ANTI-

CHOLINERGIC DRUGS

Points To Be Cover In This Presentation

 Introduction
 Classification, Mechanisms of action and Properties of Various Drugs Use to Block
Cholinergic Receptors.

PRESENTATION BY: RAVI SHARMA

QUALIFICATION: M.PHARMACY
 Nervous system

Central nervous system (CNS) Peripheral nervous system (PNS)

Autonomic nervous system (ANS) Somatic nervous system

Sympathetic nervous system Parasympathetic nervous system

 CHOLINERGIC AGENTS
• Acetyl choline (Ach) is a major neurotransmitter at autonomic,
somatic as well as central sites.
• Ach is the main physiological neurotransmitter in the cholinergic
system.
• The neurons that synthesis, store & release Ach are called cholinergic
neuron.
• Drugs that produce Parasympathetic like actions =
Parasympathomimetic = Cholinergic drugs
• Drugs that oppose Parasympathetic = Parasympatholytic =
Anticholinergic drugs
CHOLINERGIC NEURONAL MECHANISMS
 CHOLINERGIC RECEPTORS
Acetylcholine
Receptors
(Cholinoceptors)

Muscarinic (mAChR) Nicotinic (nAChR)

Smooth , cardiac muscle, brain and glands. I.e.,
Skeletal muscle,
muscle adrenal
and autonomic
medulla andganglia.
autonomic
I.e.,
muscarine (alkaloids from Amanita muscaria
stimulated
ganglia. I.e.,bystimulated
nicotine by nicotine
mushrooms

NM receptors NN receptors
M1 M2 M3 M4 M5
(muscle type) (neuronal type)
Glandular;
Glandular; causing
causing
Cardiac;
Cardiac; ↓↓ cardiac
cardiac secretion,
secretion, visceral
visceral smooth
smooth CNS; functional role CNS; functional role not Located at skeletal Located at
Neural; blocked by contractility & heart rate. contraction,
contractility & heart rate. contraction, vascular
vascular not well understood well understood muscle neuromuscular postganglionic neuron
Pirenzepine relaxation cell body
relaxation junction

Stimulatory effect on the target Inhibitory effect on the target Stimulatory effect on the target Inhibitory effect on the target Stimulatory effect on the target Stimulatory effect on the target Stimulatory effect on the target
 MECHANISMS OF ACTION OF
CHOLINOMIMETICS DRUGS
• Two modes of action:
• May directly interact with cholinergic receptors and activate them to produce
the effect.
• Increase availability of ACh at receptor sites (indirect acting).
• The availability of ACh at receptor sites is increase only by prevent its
metabolisms/hydrolysis by the enzyme choline esterase.
• Two types of choline esterase enzyme:-
• True Choline Esterase – Acetylcholinesterase
• Pseudo choline esterase – Butyrylcholinesterase
• Result: More Ach is available at the receptors and produce a
parasympathomimetic action.
MECHANISMS OF ACTION
 TWO TYPES OF CHOLINESTERASES
ENZYME
ACETYLCHOLINESTERASE Butyrylcholinesterase
(True) (Pseudo)
Distribution All cholinergic sites, RB, Plasma, liver, intestine,
Gray matter white matter

Hydrolysis of Very fast Slow

Ach
Inhibition More sensitive to More sensitive to
physostigmine organophosphates

Function Termination of Ach action Hydrolysis of ingested esters

 CLASSIFICATION
Cholinergic
drugs
Indirectly acting
Directly acting
(Anticholinesterase)

Choline esters Alkaloids Reversible Irreversible

Carbamates and Reactivation of acetylcholinesterase

Acetylcholine* Muscarine Carbamates Organophosphates Pralidoxime
Non-carbamates

Methacholine Pilocarpine Physostigmine Carbaryl Parathion

Bethanechol Arecoline Neostigmine* Propoxur Malathion

Pyridostigmin
Carbachol Nerve gases
e

Rivastigmine Dyflos

Edrophonium Echothiophate

Tacrine

To be study according to syllabus

 ACETYLCHOLINE

• Structure:-

• IUPAC name:2-acetyloxyethyl(trimethyl)azanium
• Physical Properties: White or almost white crystalline powder or
colorless crystals, very hygroscopic in nature, slightly soluble in
methylene chloride, soluble in water and alcohol.
• Storage: Stored in well closed ampolues and protect from light.
• Use: Miosis (during surgical procedure , such as cataract surgery),
cardiac depressant and effective vasodialator.
• Preparation: Ophthalmic formulation
• Brand name: Miochol
 CARBACHOL

• Structure:-

• IUPAC name: 2-[Amino carbonyl oxy]-N,N,N-trimethyl ethane ammonium

chloride
• Physical Properties: White crystalline powder, very hygroscopic in nature,
sparingly soluble in alcohol, insoluble in acetone, soluble in water.
• Storage: Stored in well closed air tight container and protect from light.
• Use: Miotic action (in the ttt of glaucoma to reduce intraocular pressure).
• Preparation: Ophthalmic formulation
• Brand name: Miostat; carbastat
 PILOCARPINE

• Structure:-

• IUPAC name: 3-Ethyl-4-[(1-methyl-imidazole-5-yl)methyl] tetrahydro-2-

furanone.
• Physical Properties: White or almost white crystalline powder or colourless
crystals, hygroscopic in nature, very soluble in water and alcohol.
• Storage: Stored in well closed air tight container and protect from light.
• Use: Use for the symptoms of dry mouth caused by radiotherapy for cancer
of head and neck and the symptoms associated with Sjogren’s syndrome.
• Preparation: Ophthalmic formulation
• Brand name: Pilocar; Salagen
 NEOSTIGMINE

• Structure:-

• IUPAC name: 3-{[(Dimethyl amino)Carbonyl]oxy}-N,N,N-trimethyl

anilinium.
• Physical Properties: White odorless crystalline powder, with bitter
taste, freely soluble in water, alcohol, and insoluble in ether.
• Storage: Stored in well closed air tight container and protect from
light.
• Use: Use for ttt of Myasthenia gravis.
• Preparation: Tablet and injection
• Brand name: Prostigmin; Myostigmin.
 EDROPHONIUM CHLORIDE

• Structure:-

• IUPAC name: Ethyl(m-hydroxy phenyl) dimethyl ammonium chloride.

• Physical Properties: White crystalline powder, soluble in water and
alcohol, and insoluble in methyl chloride.
• Storage: Stored in well closed air tight container and protect from
light.
• Use: Use as anti-arrhythmic drug, also used in diagnosis of
Myasthenia gravis
• Preparation: Injection
• Brand name: Enlon; Reversol.
 PRALIDOXIME CHLORIDE

• Structure:-

• IUPAC name: 2-Hydroxy-iminomethyl-1-methylpyridinium chloride.

• Physical Properties: Pale yellow crystalline powder, freely soluble in
water.
• Storage: Stored in well closed air tight container and protect from
light.
• Use: Use in ttt of organophosphorus insectisides
• Preparation: Injection
• Brand name: Pam; Protopam.
ECHOTHIOPATE IODIDE

I T
D O L F!
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TACRINE

I T
D O L F!
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 ANTICHOLINERGIC DRUGS
• These are those drugs which blocks the action of Acetylcholine
neurotransmitter.
• The anticholinergic drugs also called parasympatholytic agents.
• These drugs have many action like suppresses tremor and rigidity,
tachycardia, anti-secretory-antispasmodics, anti-Parkinson, rise in
body temperature due to decreased sweat.
• Mechanisms of action: The MOA of these drugs is they bind
reversibly or irreversibly with muscarinic and nicotinic receptors, and
block them.
 CLASSIFICATION
1. Natural alkaloids: Atropine, Hyoscine (Scopolamine)
2. Semisynthetic derivatives: Atropine sulphate*, methonitrate, Homatropine,
Hyoscine bromide, Ipratropium bromide, Tiotropium bromide.
3. Synthetic compounds:
A. Mydriatics: Cyclopentolate HCl, Tropicamide.
B. Vasico-selective: Oxybutynin, Flavoxate, Tolterodine, Darifenacin,
Solifenacin
C. Antiparkinsonian: Trihexyphenidyl (Benzhexol), Procyclidine, Biperiden
D. Antisecretory-antispasmodics:
a) Quaternary compounds: Propantheline, Oxyphenonium, Clidinium
bromide, Cimetropium bromide, Isopropamide, Glycopyrrolate
b) Tertiary amines: Dicyclomine HCl*, Valethamate, Pirenzepine
 ATROPINE SULPHATE

• Structure:-

• IUPAC name: 8-methyl-8-azabicyclo[3.2.1]octan-3-yl] 3-hydroxy-2-

phenylpropanoate;sulfuric acid
• Physical Properties: White crystalline powder or colorless crystals,
very soluble in water and alcohol.
• Storage: Stored in well closed container and protect from light.
• Use: Anti-muscarinic drugs; Inflammation in eye.
• Preparation: Injection, Ophthalmic, Tablet, Ointment
• Brand name: Atreza; AtroPen;
 IPRATROPIUM BROMIDE

• Structure:-

• IUPAC name: 8-methyl-8-propan-2-yl-8-azoniabicyclo[3.2.1]octan-3-yl]

3-hydroxy-2-phenylpropanoate;bromide
• Physical Properties: White or almost whie crystalline powder, freely
soluble in methanol, soluble in water, but slightly soluble in alcohol.
• Storage: Stored in well closed container and protect from light.
• Use: Acute asthmatic attack.
• Preparation: Nebulizer solution; Pressurized inhalation; Powder for
inhalation
• Brand name: Atrovent; Atrovent HFA; Ipratropium Inhalation Solution;
Ipratropium Inhalation Aerosol.
 CYCLOPENTOLATE HCl

• Structure:-
• IUPAC name: 2-(Dimethylamino) ethyl-1-hydroxyl-α-phenyl
cyclopentane acetate hydrochloride.
• Physical Properties: White or almost white crystalline powder, soluble
in methanol, water and ethanol.
• Storage: Stored in well closed container and protect from light.
• Use: Mydriasis.
• Preparation: Eye drops
• Brand name: Cyclopent; Cyclate; Dialate
 TROPICAMIDE

• Structure:-
• IUPAC name: N-Ethyl-2-phenyl-N-(4-pyridylmethyl)-3-hydroxy-
propionamide
• Physical Properties: White or almost white crystalline powder, soluble
in alcohol and methylene blue, and slightly soluble in water.
• Storage: Stored in well closed air tight container and protect from light.
• Use: Mydriasis.
• Preparation: Eye drops
• Brand name: Tropicamet; Tmide Ed; Optimide
 CLIDINIUM BROMIDE

• Structure:-
• IUPAC name: (1-methyl-1-azoniabicyclo[2.2.2]octan-3-yl) 2-hydroxy-2,2-
diphenylacetate;bromide
• Physical Properties: White crystalline powder, soluble in water and
chloroform.
• Storage: Stored in well closed air tight container and protect from light.
• Use: Bronchodilator in asthmatic conditions; ttt of peptic ulcer;
antispasmodic
• Preparation: Tablet and capsule
• Brand name: Librax
 DICYLCLOMINE HCl

• Structure:- 2-(Diethylamino) ethyl bicyclohexyl-1-carboxylate; HCl

• IUPAC name: (1-methyl-1-azoniabicyclo[2.2.2]octan-3-yl) 2-hydroxy-2,2-
diphenylacetate;bromide
• Physical Properties: White crystalline powder with bitter in taste,
soluble in water and chloroform.
• Storage: Stored in well closed air tight container and protect from light.
• Use: Antispasmodic
• Preparation: Tablet
• Brand name: Bentyl; Mesbentyl
 a n k
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