Chapter-6 | P.

Chemistry

Drugs Acting on Autonomic Nervous System

In Syllabus:

Study of the following category of medicinal compounds with respect to

classification, chemical name (IUPAC Name), chemical structure
(compounds marked with*) uses, stability and storage conditions, different
types of formulations and their popular brand names:

Drugs Acting on Autonomic Nervous System

Sympathomimetic Agents (Adrenergic

Agonists)
Direct Acting Agents:
• Nor-epinephrine, * Phenylephrine, Terbutaline, Naphazoline, *
Epinephrine, Dopamine, * Salbutamol, Tetrahydrozoline
Indirect Acting Agents:
• Hydroxy amphetamine, Pseudoephedrine
Mixed Acting Agents:
• Ephedrine, Metaraminol
Adrenergic Antagonists (Sympatholytic Agents)
Alpha Adrenergic Blockers:
• Tolazoline, Phentolamine, Phenoxybenzamine, Prazosin.
Beta Adrenergic Blockers:

• Propranolol, * Atenolol, * Carvedilol

Cholinergic Drugs and Related Agents
(PARASYMPATHOMIMETIC)

Direct Acting Agents

• Acetylcholine, * Carbachol, Pilocarpine.

Cholinesterase Inhibitors (Indirect Acting Agents)

• Neostigmine, * Edrophonium chloride, Tacrine hydrochloride,

Echothiopate iodide.
Cholinergic Blocking Agents (Cholinergic Antagonists)

• Atropine sulphate, * Ipratropium bromide.

Synthetic Cholinergic Blocking Agents

• Tropicamide, Cyclopentolate hydrochloride, Clidinium bromide,

and Dicyclomine hydrochloride. *

Drugs Acting on Autonomic Nervous System:

• Drugs acting on the autonomic nervous system (ANS) are a class of
medications that affect the involuntary control of certain bodily
functions, such as heart rate, blood pressure, and digestion.
• These drugs can either inhibit or enhance the functions of the
parasympathetic and sympathetic nervous systems.

Sympathomimetic agents (adrenergic agonists)

Sympathomimetics, also called adrenergic drugs or adrenomimetics or
adrenergic stimulants are the drugs that elicit effects, like obtained from
the stimulation of adrenergic nerves. It means, these have effects like, or
the same as, epinephrine (adrenaline).

These show its biological action through receptor mechanism. For

example, these bind with at least two different types of receptors (α and
ß), each having two subclasses.

Adrenergic agonist is a drug that binds to and activates adrenergic

receptors. Adrenergic receptors are proteins found on the surface of cells
throughout the body. When activated, these receptors send signals to the
cells, causing them to change their activity.
There are two main types of adrenergic receptors: alpha receptors and
beta receptors. Alpha receptors are further divided into alpha-1 and
alpha-2 receptors, while beta receptors are further divided into beta-1,
beta-2, and beta-3 receptors.

Classification of Sympathomimetic Agents

According to the mode of action, these are classified into three types:

1. Direct acting sympathomimetic drugs: These act through interaction

with specific receptors, e.g., epinephrine, nor epinephrine.

2. Indirect acting sympathomimetic drugs: These act either by

releasing catecholamines, mainly nor epinephrine from storage granules
or through inhibition of nor epinephrine uptake at neuronal membrane.
Release of norepinephrine or inhibition of uptake of norepinephrine leads
to desired action. This class of drugs is represented by tyramine. Hydroxy
amphetamine and pseudoephedrine are the other examples.

3. Mixed action type sympathomimetic drugs: They act by both

mechanisms described above. e.g., Ephedrine and Amphetamine.
 Chemically, these are classified into:

(i) Catecholamines (contain catechol nucleus), e.g., epinephrine, nor

epinephrine, isoprenaline

(ii) Non-catecholamines (do not contain catechol nucleus), e.g.,

salbutamol, terbutaline, phenylephrine, orciprenaline, etc

Nor-epinephrine, *

• Norepinephrine, also known as noradrenaline, is both a

neurotransmitter and a hormone. It plays an important role in your
body's “fight-or-flight” response.
• It is a primary amine, differs from epinephrine in not possessing
methyl group attached to N-atom.

Chemical Name:

4-[(1R)-2-amino-1-hydroxyethyl] benzene-1,2-diol

Properties:

It is used as a tartrate salt which is white or faintly grey, odourless

crystalline powder with bitter taste, soluble in water and insoluble in ether

and chloroform. It is easily metabolized by MAO and COMT and thus not

effective orally.
Chemical Structure:

Uses:
• As a medication, norepinephrine is used to increase and maintain
blood pressure in limited, short term serious health situations.

Stability and storage conditions:

• Solutions of norepinephrine should be stored in PVC bags at 4°C for

61 days with protection from light.

Types of formulations:

• Injectable solution
Popular brand names:
• Levarterenol, Levophed, Norepin, Adrenor, Adronis, Nestig, Nodresol

Epinephrine,
• Epinephrine (Adrenaline) is an endogenous hormone and medication,

normally produced by both the adrenal glands and a small number of

neurons in the medulla oblongata, where it acts as a neuro-transmitter

involved in regulating visceral functions (e.g., respiration). It acts via

receptor mechanism by binding to alpha and beta receptors.

Chemical Name:

4-[(1R)-1-hydroxy-2-(methylamino)ethyl]benzene-1,2-diol

Properties:

• It is white, odourless, crystalline powder, very slightly soluble in water

and alcohol. Its salt (tartrate, borate) is readily soluble in water. Due to

presence of catechol moiety, it darkens on exposure to light and air.

Hence, sodium bisulphite is often used in preparation of epinephrine

to prevent the oxidation by air/oxygen.

Uses:

• It is used to relieve bronchospasm in acute asthmatic activity but not

effective on oral administration.
• It is used intravenously. Its use in the treatment of heart attack or
circulatory collapse is limited because of its tendency to induce
cardiac arrhythmias.
• It is used in the treatment of open angle glaucoma where it apparently
reduces intraocular pressure by increasing the rate of outflow of
aqueous humour from the anterior chamber of the eye.
• Common side effects include shakiness, anxiety, and sweating. A fast
heart rate and high blood pressure may occur.

Stability and storage conditions:

• It should be kept in a cool, dry place and stored at room

temperature. Direct sunlight is prohibited.
Types of formulations:

• Injection solution, Ophthalmic solution, Aerosol inhaler, Nasal

solution, Nebuliser inhaler

Popular brand names:

• EpiPen, Adrenaclick, epifrin

Phenylephrine

• Phenylephrine selectively binds to α1 receptors which cause blood

vessel to constrict. Chemically it differs from adrenaline only in
lacking a hydroxyl group at C4 position of benzene ring.

Chemical Name:

• (R)-3-[-1-hydroxy-2-(methylamino)ethyl] phenol

Uses:
• It is also used to relieve sinus congestion and pressure.
• Phenylephrine will relieve symptoms but will not treat the cause of the
symptoms or speed recovery.
• Phenylephrine is used to relieve nasal discomfort caused by colds,
allergies, and hay fever.
• It is also used to dilate the pupil and to relieve haemorrhoids.

Stability and storage conditions:

• It should be kept in a cool, dry place and stored at room

temperature. Direct sunlight is prohibited.

Types of formulations:

• Nasal Drop, Solution, Tablets, Injection

Popular brand names:

• Nostril, Pretz-D, Rhinall, Tur-Bi-Cal, Alconefrin-12, Vibroal

Dopamine*
• Dopamine is a type of neurotransmitter and hormone. It plays a role in
many important body functions, including movement, memory and
pleasurable reward and motivation.
• High or low levels of dopamine are associated with several mental
health and neurological diseases.
• Dopamine (a central neurotransmitter) is a metabolic precursor of nor-
epinephrine and epinephrine. It does not cross the blood brain barrier
and thus has minimal effect on the CNS.
• It acts on the receptors and produces a positive inotropic effect on
heart. It increases the systolic and pulse pressures.

Chemical Name:

4-(2-aminoethyl) benzene-1,2-diol

Chemical Structure:

Uses:
• Dopamine is administered as a continuous intravenous infusion.
At low doses, dopamine preferentially stimulates D1 and D2
receptors in the renal vasculature, which leads to vasodilation and
promotes renal blood flow to preserve glomerular filtration.
• Dopamine is a peripheral Vaso stimulant used to treat low blood
pressure, low heart rate, and cardiac arrest.
• Dopamine (Intropin) is used to treat shock and low blood pressure
caused by heart attack, trauma, infections, or surgery.
• It is used in acute congestive heart failure with imminent renal failure.
• It is used in acute pancreatitis.

Stability and storage conditions:

• It should be kept in a cool, dry place and stored at room

temperature. Direct sunlight is prohibited.
Types of formulations:
• Injectable solution

Popular brand names:

• Intropin

Terbutaline,

Terbutaline is in a class of medications called beta agonists. It works by

relaxing and opening the airways, making it easier to breathe.

Chemical Name:
(RS)-5-[2-(tert-Butylamino)-1-hydroxyethyl] benzene-1,3-diol
Uses:
• Terbutaline is used to prevent and treat wheezing, shortness of
breath, and chest tightness caused by asthma, chronic bronchitis,
and emphysema.

Stability and storage conditions:

 • It should be kept in a cool, dry place and stored at room
temperature. Direct sunlight is prohibited.

Types of formulations:

• Powder, Solution
Popular brand names:

• Brethaire, Brethine

Salbutamol,
• It, also known as albuterol, is a short-acting, selective β2-

adrenergic receptor agonist used in the treatment of asthma and

chronic obstructive pulmonary diseases (COPD). It is 29 times

more selective for β2-receptors than β1-receptors giving it higher

specificity for pulmonary β receptors in comparison to β1-

adrenergic receptors located in the heart.

Chemical Name:

(RS)-4-[2-(tert-Butylamino)-1-hydroxyethyl]-2-(hydroxymethyl)phenol

Properties:

• Salbutamol is white or almost white, crystalline powder; sparingly

soluble in water; soluble in ethanol; slightly soluble in ether. It is

available as sulphate salt which is odourless powder with slightly

bitter in taste, very soluble in water.

Chemical Structure:
Uses:

• Salbutamol is typically used to treat bronchospasm (due to any cause

allergic asthma or exercise-induced), as well as chronic obstructive
pulmonary disease. As a B, agonist, salbutamol also has use in
obstetrics.
• Intravenous salbutamol can be used as a tocolytic to relax the uterine
smooth muscle to delay premature labor.
• Common side effects include shakiness, headache, fast heart rate,
dizziness, and feeling anxious.

Stability and storage conditions:

• It should be kept in a cool, dry place and stored at room temperature.
Direct sunlight is prohibited.

Types of formulations:

• Tablet, capsule, syrup, and aerosol inhaler.

Popular brand names:

• Ventolin, Airomir, Asmalal, Easyhaler, Pulvinal, Salamol, Easi-

Breathe, Salbulin, asthalin

Naphazoline*
• It is imidazole derivative and sympathomimetic with marked α-
adrenergic activity. It is partial agonist at both α1 and α2 adrenergic
receptor.

Chemical Name:
2-(naphthalen-1-ylmethyl)-4,5-dihydro-1H-imidazole

Properties:

• Naphazoline is used as hydrochloride or nitrate salts. Naphazoline HCl

is a white crystalline odourless powder with bitter taste. The salt is
freely soluble in water and alcohol.

Uses:

• It is mainly used as nasal decongestant to relieve redness, puffiness,

and itchy/water eyes due to cold, allergy or eye irritation. It is
commonly available in ophthalmic drop formulation.
• Common side effects are mild burning of the eye, blurred vision,
watery eyes, mild headache, dizziness, nervousness.

Stability and storage conditions:

• It should be kept in a cool, dry place and stored at room

temperature. Direct sunlight is prohibited.
Types of formulations:

• Nasal Drops, Ophthalmic gel forming solution, Ophthalmic

solution
Popular brand names:

• Naphcon-A, vasocon
Tetrahydrozoline:
• Tetryzoline, also known as tetrahydrozoline, is a derivative of
imidazoline with central and peripheral alpha (α)-adrenergic
properties.
• Tetryzoline is a drug used in some over-the-counter eye drops and
nasal sprays.
Chemical Name:

(RS)-2-(1,2,3,4-tetrahydronaphthalen-1-yl)-4,5-dihydro-1H-imidazole

Chemical Structure:

Uses:
• Ophthalmic tetrahydrozoline is used to relieve minor eye irritation and
redness caused by colds, pollen, and swimming.

Stability and storage conditions:

• It should be kept in a cool, dry place and stored at room temperature.

Direct sunlight is prohibited.
Types of formulations:

• Eye Drops, nasal solution

Popular brand names:

• Visine, eyesine
Indirect Acting Agents:

• Hydroxyamphetamine,
• Pseudoephedrine

Hydroxyamphetamine:
• 4-Hydroxyamphetamine acts as an indirect sympathomimetic and
causes the release of NE from nerve synapses which leads to
mydriasis (pupil dilation). It is also a major metabolite of
amphetamine and certain substituted amphetamines.
• 4-Hydroxyamphetamine, also known as hydroxyamfetamine, is a
drug that stimulates the sympathetic nervous system.
• It is used medically in eye drops to dilate the pupil, so that the back
of the eye can be examined.
Chemical Name:

Hydroxyamphetamine hydrobromide

Uses:

• It also reduces your body's ability to adjust your eye for near vision.
These drops are used when you have your eyes examined by the eye
doctor.
• Side effects include allergic reaction, irregular or fast heart rate or
high blood pressure

Stability and Storage conditions:

• It should be kept in a cool, dry place and stored at room

temperature. Direct sunlight is prohibited.
Types of formulations:

• Eye Drops
Popular Brand Name:

• Paremyd, paredrine

Pseudoephedrine:

• Pseudoephedrine is a sympathomimetic drug of the

phenethylamine and amphetamine chemical classes.
• It may be used as a nasal/sinus decongestant, as a stimulant, or as
a wakefulness-promoting agent in higher doses.

Chemical Name:
(S,S)-2-methylamino-1-phenylpropan-1-ol
Uses:
• Pseudoephedrine is used to relieve nasal congestion caused by
colds, allergies, and hay fever.
• It is also used to temporarily relieve sinus congestion and pressure.
Stability and Storage conditions:

• It should be kept in a cool, dry place and stored at room

temperature. Direct sunlight is prohibited.

Type of formulation:
• Tablet
• Capsule
• Aerosol
• Inhaler
Popular Brand Name:
• Sudafed, Galpseud, Boots Decongestant
Mixed Acting Agents:
• Ephedrine, Metaraminol

Ephedrine:
It is a naturally occurring alkaloid with phenylethylamine skeleton, isolated
from ephedra species. It has 2 asymmetric carbon atoms, thus there are 4
optically active isomers. The erythro isomer is called ephedrine which has
both α and ß adrenergic agonistic activity. The threo isomer is called
pseudoephedrine.

Chemical Name:
benzenemethanol α - [1 - (methylamino) ethyl] - sulfate (2:1) (salt).
Chemical Structure:

Properties:

• It exists as a solid, slightly soluble in water and a very weakly acidic

compound. It is official as ephedrine sulphate and ephedrine
hydrochloride salts. Both are white crystalline powder, soluble in
water and alcohol.

Uses:

• Ephedrine is a medication used to manage and treat clinically

significant hypotension. It is in the sympathomimetic class of drugs.
 • Ephedrine is a central nervous system stimulant that is often used to
prevent low blood pressure during anaesthesia.
• It has also been used for asthma, narcolepsy, and obesity but is not the
preferred treatment.
• It is of unclear benefit in nasal congestion.

Stability and Storage conditions:

It is stored at room temperature, between 15 and 25°C away from extreme
heat, moisture, and light as it becomes dark in colour.

Type of formulation:
Nasal solution, capsule, injection
•
Brand Name:

• Akovaz, Corphedra, Emerphed

Metaraminol:
• Metaraminol is a sympathomimetic agent with direct and indirect
effects on adrenergic receptors.
It has both alpha and beta-adrenergic activity, the former being
predominant.
• Metaraminol increases the force of myocardial contractions as well as
having a peripheral vasoconstrictor action.

• It, also known as metaradrine, is a stereoisomer of meta-hydroxy

norephedrine. It is a potent sympathomimetic amine that increases
both systolic and diastolic blood pressure. It is an α1-adrenergic
receptor agonist with some β effect.

Chemical Name:
(1R,2S)-3-[-2-amino-1-hydroxy-propyl] phenol

Chemical Structure:

Properties:

It is available as Metaraminol bitartrate which is a white crystalline powder;

freely soluble in water; slightly soluble in alcohol, and practically insoluble
in chloroform and in ether.

Uses:
• Metaraminol is indicated for prevention and treatment of the acute
hypotensive state occurring with spinal anaesthesia.

Stability and Storage conditions:

• It should be kept in a cool, dry place and stored at room temperature.
Direct sunlight is prohibited.
Type of formulation:
• Injection

Brand Name:

• Aramine, Metaramin, Pressonex

Adrenergic antagonists (sympatholytic agents):

• Adrenergic antagonists are also referred to as sympatholytics
because they lyse, or block, the effects of the sympathetic nervous
system.
• They react with specific adrenergic receptor sites without activating
them, thus preventing the typical manifestations of SNS activation.
Classification:
1. α-adrenergic receptor antagonist:
i. Non-selective α receptor antagonist
a. Haloalkylamines (Phenoxybenzamine)
b. Imidazolines (Tolazoline, Phentolamine)
ii. α1- selective antagonists (Prazosin, Terazosin and Doxazosin)
iii. α2- selective antagonists (Yohimbine)
iv. Ergot alkaloids (Ergotamine)
2. β adrenergic receptor antagonist:
i. Non-selective adrenergic receptor antagonist
ii. Cardioselective β1 receptor antagonist.
Alpha Adrenergic Blockers:
• Tolazoline,
• Phentolamine,
• Phenoxybenzamine,
• Prazosin.

Tolazoline:
• Tolazoline is a reversible non-selective competitive α-adrenergic
receptor antagonist.
• It is a vasodilator that is used to treat spasms of peripheral blood
vessels.
Chemical Name:
2-Benzyl-4,5-dihydro-1H-imidazole

Chemical Structure:
Uses:
• Tolazoline is a vasodilator used to treat pulmonary artery anomalies.
• It is indicated for use in persistent pulmonary hypertension of
newborn when supportive measures are not successful.
Stability and Storage conditions:
• It should be kept in a cool, dry place and stored at room temperature.
Direct sunlight is prohibited.
Type of formulation:
• Syrup
• Tablet
• Injectable solution
Brand Name:

• Priscoline

Phentolamine:
• Phentolamine is a reversible, long-acting, adrenergic, alpha-receptor
blocking agent which can produce and maintain "chemical
sympathectomy" by oral administration.
• It increases blood flow to the skin, mucosa, and abdominal viscera,
and lowers both supine and erect blood pressures.
Chemical Name:
3-[(4,5-Dihydro-1H-imidazol-2-ylmethyl)(4-methylphenyl)amino]phenol
Chemical Structure:

Properties:

• It is used as mesylate salt, which is white, odourless, crystalline

powder with bitter taste, soluble in water (1:1) and slightly soluble in
alcohol.
Uses:
• Phentolamine is indicated for the control of episodes of hypertension
and sweating that occur with a disease called pheochromocytoma.
Stability and Storage conditions:
• It should be kept in a cool, dry place and stored at room temperature.
Direct sunlight is prohibited.
Type of formulation:
• Powder for injection,
• Injection Solution

Brand Name:

• Regitine,
• OraVerse
Phenoxybenzamine:
• It is a prototype drug of haloalkylamines class.

• It is in the nonselective, irreversible antagonist of the alpha-adrenergic

receptors class of drugs.

Chemical Name:

N-(2-chloroethyl)-N-(1-methyl-2-phenoxyethyl) benzylamine

Chemical Structure:

Properties:

• It is a colourless crystalline compound, soluble in alcohol, water, and

chloroform.
Uses:
• Phenoxybenzamine is a medication used in the management and
treatment of paroxysmal hypertension and sweating resulting from
pheochromocytoma.
Stability and Storage conditions:
• It should be kept in a cool, dry place and stored at room temperature.
Direct sunlight is prohibited.
Type of formulation:
• Capsule
• Tablet

Brand Name:

• Dibenzyline
• Fenoxen
Prazosin:
• It is a quinazoline derivative that acts as a competitive alpha1-
antagonist.
• It is active after oral administration and has minimal effect on cardiac
function due to selectivity towards alpha-1 adrenergic receptor.
Chemical Name: [4-(4-Amino-6,7-dimethoxy-2-quinazolinyl)-1-

piperazinyl] (2-furyl)methanone

Chemical Structure:

Properties:

• It is white, crystalline substance, slightly soluble in water and isotonic

solution.
Uses:
• Prazosin is used alone or in combination with other medications to
treat high blood pressure.
• It is used for treating enlarged prostate and PTSD.
• Common side effects include dizziness, sleepiness, nausea and heart
palpitations.
Stability and Storage conditions:
• It should be kept in a cool, dry place and stored at room temperature.
Direct sunlight is prohibited.
Type of formulation:
• Capsules

Brand Name: Minipress, Vasoflex, Lentopress

Adrenergic Antagonists (Sympatholytic Agents)

Beta Adrenergic Blockers:

• Propranolol*, Atenolol*, Carvedilol

Propranolol:
• It is a non-selective beta blocker, having naphthalene as basic
skeleton.
• Propranolol is a type of medicine called a beta blocker. Like other beta
blockers, propranolol works by changing the way your body responds
to some nerve impulses, including in the heart.
• It slows down your heart rate and makes it easier for your heart to
pump blood around your body.
Chemical Name:
6-Chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide-1,1-
dioxide.
Chemical Structure:

Properties:

• It is available as hydrochloride salt which is white, odourless

crystalline powder, soluble in 1 in 20 of water or alcohol, slightly
soluble in chloroform, practically insoluble in ether.
Uses:
• It's used in the treatment of angina pectoris, hypertension, myocardial
Infarction, hypertrophic cardiomyopathy, pheochromocytoma,
migraine prophylaxis and emotional tremor.
• It is contraindicated in presence of conditions like asthma and
bronchitis.
• Common side effects include nausea, abdominal pain, constipation.
Stability and Storage Conditions:
• It should be kept in a cool, dry place and stored at room temperature.
Direct sunlight is prohibited.
Type of formulation:
• Capsules
• Tablet
• Solution
• Injection
Brand Name:

• Inderal LA,
• Innopran XL,
• Inderal XL
• Ciplar

Atenolol:
• Atenolol is a peripheral, cardio selective beta blocker specific for
beta-1 adrenergic receptors, without intrinsic sympathomimetic
effects.
• Atenolol is a beta blocker medication primarily used to treat high
blood pressure and heart associated chest pain.
• Atenolol, however, does not seem to improve mortality in those with
high blood pressure.
Chemical Name:
[4-[2-hydroxy-3-isopropyl-aminopropoxy]-phenyl-acetamide]

Chemical Structure:
Properties:

• It is available as white solid powder. It is soluble in water, freely soluble

in 1N HCl and less soluble in chloroform.

Uses:
• Atenolol is used alone or in combination with other medications to
treat high blood pressure.
• It also is used to prevent angina (chest pain) and improve survival after
a heart attack.
• It is also used in therapy following myocardial infarction.
Stability and Storage Conditions:
• It should be kept in a cool, dry place and stored at room temperature.
Direct sunlight is prohibited.
Type of formulation:
• Capsule
• Tablet
• injection
Brand Name:

• Tenormin, Atelol, betacard

Carvedilol:
• Carvedilol is a type of medicine called a beta blocker. Carvedilol, sold
under the brand name Coreg among others, is a medication used to
treat high blood pressure, congestive heart failure, and left ventricular
dysfunction in people who are otherwise stable.
Chemical Name:
((2RS)-1-(9H-carbazol-4-yloxy)-3-[[2-(2-methoxyphenoxy)

ethyl]amino]propan-2-ol)
Chemical Structure:

Properties:

• Carvedilol phosphate is available as colourless solid, soluble in

methylene chloride, methanol, sparingly soluble in ethanol,
isopropanol, slightly soluble in ethyl ether.
Uses:
• It is used to treat high blood pressure (hypertension), Congestive heart
failure, left ventricular dysfunction in people who are otherwise
stable.
Stability and Storage Conditions:
• It should be kept in a cool, dry place and stored at room temperature.
Direct sunlight is prohibited.
Type of formulation:
• Tablet

Brand Name:

• Coreg
Cholinergic drugs and related agents (parasympathomimetic)

• Cholinergic drugs show the same actions as obtained from the

stimulation of PNS. The pharmacological actions are mediated in PNS

through Acetylcholine (Neurotransmitter).

• Acetylcholine exerts its action through two types of receptors:

Nicotinic and muscarinic receptors.

• The name nicotinic and muscarinic has been given based on response

produced by cholinergic receptors towards two alkaloids nicotine

(principal alkaloid of tobacco plant) and muscarine (component of

mushroom).

Direct Acting Agents

• Acetylcholine, * Carbachol, Pilocarpine.

Acetylcholine:
• Acetylcholine is the neurotransmitter at neuromuscular junctions, at
synapses in the ganglia of the visceral motor system, and at a variety
of sites within the central nervous system.
Chemical Name: 2-Acetoxy-N,N,N-trimethylethanaminium
Chemical Structure:

Properties and uses: It is a white or almost white crystalline powder or

colourless crystals, very hygroscopic in nature, slightly soluble in methylene
chloride, soluble in water and alcohol. It is a topical ophthalmic drug to
induce miosis, during certain intraocular surgical procedures, such as
cataract surgery, iridectomy, penetrating keratoplasty, and other anterior-
segment surgery. Systemically administered Ach is rapidly hydrolysed by
acetylcholinesterase, hence, it has no clinical use. It is a cardiac depressant
and effective vasodilator.

Storage: It should be stored in well closed ampoules and protected from

light.
Types of Formulations
• Powder for injection,
• Gels,
• Lozenges

Carbachol:
Chemical Name: 2-[(Aminocarbonyl)oxy]-N,N,N-trimethylethanaminium

chloride

Chemical Structure:

Properties and uses: It is a white crystalline, hygroscopic powder, soluble in

water, sparingly soluble in alcohol, insoluble in acetone. It is an ester of
carbamic acid, the terminal methyl group of Ach is replaced by amino group.
It possesses both muscarinic and nicotinic properties by cholinergic
receptor stimulation. It is more slowly hydrolysed by acetylcholinesterase. It
is used for its miotic actions in the treatment of glaucoma to reduce
intraocular pressure.
Storage: It should be stored in well-closed airtight containers and protected
from light.
Dose: Topically 0.1 ml of 0.75 to 3% solution.
Type of Formulation:
• Tablet,
• Solution

Brand Name: Miostat, Carcholin

Pilocarpine.
Chemical Name: 3-Ethyl– 4 –[(1-methyl-imidazole-5-yl)methyl] tetrahydro-

2-furanone

Properties and uses: It is a white or almost white crystalline powder or

colourless crystals, hygroscopic, very soluble in water and in alcohol.
Pilocarpine is an alkaloid obtained from the dried leaflets of Pilocarpus
jaborandi and Pilocarpus microphyllus in which it occurs to the extent of
about 0.5% together with other alkaloids. Pilocarpine is a nonselective
agonist on the muscarinic receptors. It acts on M3 receptors in smooth
muscles and cause contractions in the gut, trachea, and eyes. It is used for
the treatment of symptoms of dry mouth caused by radiotherapy for cancer
of head and neck and the symptoms associated with Sjogren’s syndrome.
Storage: It should be stored in well-closed airtight containers and
protected from light.
Dose: Topically 0.1 ml of 0.5 to 6% solution into the conjunctival sac 1 to 5

times/day.

Dosage forms: Pilocarpine hydrochloride eye drops B.P.

Brand Name:

• Pilicar
• Carpine
• Locarp

Cholinesterase Inhibitors (Indirect Acting Agents)

• Cholinesterase inhibitors (ChEIs) are a class of drugs that inhibit the
activity of acetylcholinesterase, an enzyme that breaks down the
 neurotransmitter acetylcholine. This leads to an accumulation of
acetylcholine in the synaptic cleft, which enhances cholinergic
transmission.
• ChEIs are used to treat a variety of conditions, including Alzheimer's
disease, myasthenia gravis, and glaucoma.
• They are also used as antidotes for poisoning by organophosphates
and carbamates.
• Indirect acting cholinesterase inhibitors are a type of ChEI that work
by increasing the amount of acetylcholine available at the
neuromuscular junction.
• This is done by inhibiting the breakdown of acetylcholine by
acetylcholinesterase. Indirect acting ChEIs include neostigmine,
pyridostigmine, and ambenonium.
Example:
• Neostigmine, * Edrophonium chloride, Tacrine hydrochloride,
Echothiophate iodide.

Neostigmine, *
• Neostigmine is water-soluble, an ionized compound that reversibly
inhibits the enzyme acetylcholinesterase.
Chemical Name:

3-{[(Dimethyl amino) carbonyl] oxy}-N, N, N-trimethyl benzene ammonium

Chemical Structure:

Properties: It exists as white, odourless, crystalline powder with a bitter

taste, freely soluble in water, alcohol, and insoluble in ether. Its solutions are
neutral to litmus. It acts as a cholinesterase inhibitor.
Storage: It should be stored in well-closed airtight container and protected
from light.
Dosage forms: Neostigmine bromide tablets I.P., Neostigmine methyl
sulphate injection I.P., Neostigmine tablets B.P.
Uses:
• Neostigmine injection is used to treat a muscle disease called
myasthenia gravis.
• Neostigmine injection is also used to prevent or treat certain kidney or
intestinal problems.
• This medicine is also given after surgery to help reverse the effects of
certain types of medicines that have been used to relax the muscles.
Brand Name:

• Prostigmine, Myostigmin, Tilstigmin

Edrophonium chloride:
Chemical Name:
Ethyl (m-hydroxy phenyl) dimethyl ammonium chloride

Properties and uses: It exists as a white crystalline powder, soluble in water

and alcohol, insoluble in methylene chloride. On parenteral administration,
edrophonium has a more rapid onset and shorter duration of action than
neostigmine, pyridostigmine, or ambenonium. It is used as an antiarrhythmic
drug in paroxymal atrial tachycardia. It is also used in the diagnosis of
myasthenia gravis.
Storage: It should be stored in well-closed airtight containers and protected
from light.
Dose: By I.V. 2 to 10 mg; usually 2 mg is injected initially and if no adverse

reaction takes place within 30 sec, the remaining 8 mg may be injected.

Dosage form: Edrophonium injection B.P.

Brand Name:

• Tensilon
Tacrine hydrochloride,
Chemical Name:

Properties and its uses: It is a parasympathomimetic and a centrally acting

cholinesterase inhibitor (anti-cholinesterase). It was the first centrally acting

cholinesterase inhibitor approved for the treatment of AD and was marketed

under the trade name Cognex.

Stability and Storage Conditions:

• It should be kept in a cool, dry place and stored at room temperature.
Direct sunlight is prohibited.
Type of Formulation:
• Tablet

Brand Name:

• Cognex®

Pralidoxime Chloride
Chemical Name:
• 2-Formyl-1-methyl pyridinium chloride oxime
Properties and uses: It exists as a white to pale yellow crystalline powder,
odourless, soluble in water. Used as an antidote for parathion and related
pesticides poison.
Stability and Storage conditions: It is chemically intact for up to 48 hour
after injection. Keep container tightly closed in a dry and well-ventilated
place.
Dosage form: Injection (IV)
Brand name: Protocam chloride (Baxter), Duodote
Echothiophate iodide.

Chemical Name:

2-[(Diethoxyphosphonyl) thio] N,N,N-trimethyl ethan ammonium

iodide

Properties and uses: It exists as white crystalline hygroscopic solid with

slight mercaptan-like odour, soluble in water, methanol, or dehydrated
alcohol, but insoluble in organic solvents. It is a long-acting irreversible anti-
AchE drug, used in the treatment of glaucoma.
Dose: Topically for adult in the treatment of glaucoma, 1 drop of 0.03% to
0.25% solution.
Stability and Storage Conditions:
• Store the unmixed product in the refrigerator away from light and
moisture. Do not freeze.
• The mixed solution may be stored at room temperature for up to 4
weeks. Do not refrigerate the mixed solution.
Type of Formulation:
• Eye Drops

• Brand Name:

• Phospholine Iodide
CHOLINERGIC BLOCKING AGENTS (CHOLINERGIC ANTAGONISTS)
• Atropine sulphate, * Ipratropium bromide.

Atropine sulphate:
Chemical Name:

Chemical Structure:

Properties and uses: It is a white crystalline powder or colourless crystals,

freely soluble in alcohol and well soluble in water. It is the tropine ester of
racemic tropic acid and is optically inactive. The greater molar potency of
atropine helps it to block several moles of acetylcholine. The umbrella-like
atropine molecule may mechanically or electrostatically inactivate adjacent
receptors on the cell surface so that these receptors are also unavailable for
acetylcholine or other parasympathomimetic stimulants. Atropine has all
the actions and uses of antimuscarinic drugs.
Stability and Storage Conditions:
• It should be kept in a cool, dry place and stored at room temperature.
Direct sunlight is prohibited.
Dose: In Bradycardia: Adult: 500 μg every 3–5 min totally 3 mg.
Dosage forms: Atropine methonitrate injection I.P., Atropine sulphate
injection I.P., Atropine sulphate tablets I.P., Atropine sulphate ointment
I.P., Atropine Eye drops B.P., Atropine Eye ointment B.P., Atropine
injection B.P., Atropine tablets B.P., Morphine and Atropine injection B.P.

Brand Name: Atp, Tropine

Ipratropium Bromide

Chemical Name:
(±)-endo-3-(3-Hydro-1-oxo-2-phenyl propyl)-8-methyl-8-(1-methyl ethyl-
8-azoniabicyclo octane bromide

Properties and uses: It is a white or almost white crystalline powder,

freely soluble in methanol, soluble in water, but slightly soluble in
ethanol. It is used in the inhalation therapy to produce dilation of
bronchial smooth muscle for acute asthmatic attacks. It produces
broncho-dilation by competitive inhibition of cholinergic receptors
bound to the smooth muscles of the bronchioles.

Storage: It should be stored in well-closed airtight containers, protected

from light.

Dose: For inhalation reversible airways obstruction and COPD,

maximum dose is 320 μg daily as nebulized solution.

Dosage forms: Ipratropium Nebuliser solution B.P., Ipratropium powder

for inhalation B.P., Ipratropium pressurized inhalation B.P.
Brand Name: Ipneb, Ipranaseaq, Ipratop

SYNTHETIC CHOLINERGIC BLOCKING AGENTS

Tropicamide

Chemical Name:
N-Ethyl-2-phenyl-N-(4-pyridylmethyl)-3-hydroxy-propionamide

Properties and uses: It is a white or almost white crystalline powder,

soluble in alcohol and methylene chloride, but slightly soluble in water.
Used to induce mydriasis and cycloplegia in ophthamologic practice and
it has short duration of action.
Storage: It should be stored in well-closed airtight containers and
protected from light.

Dose: The usual adult topical dose is 1 to 2 drops of a 0.5% or 1% solution

to the conjunctiva; for mydriasis 0.5% solution is employed, and for
cycloplegia 1% solution.

Dosage forms: Tropicamide eye drops I.P., B.P.

Brand Name: Tropicamet, Tmide Ed, Optimide

Cyclopentolate Hydrochloride

Chemical Name:
2-(Dimethylamino) ethyl-1-hydroxyl-α-phenyl cyclopentane acetate
hydrochloride

Properties and uses: It exists as white crystalline powder, soluble in

water, methanol, and ethanol, but insoluble in toluene. Cyclopentolate is
usually employed as eye drops to cause cycloplegia and mydriasis. It
acts much faster than atropine and possesses a relatively shorter
duration of action.

Dose: Topically for adult, 1 drop of 1 or 2% solution to the conjunctiva; for

refraction 1 drop of a 0.5% solution repeated after 5 to 15 min.

Dosage forms: Cyclopentolate eye drops B.P.

Brand Name: Cyclopent, Cyclate, Dilate

 Clidinium Bromide

Chemical Name:
3-OH-1-Methyl quinuclidium bromide benzilate

Uses: Used as a bronchodilator in asthmatic conditions. It has a longer

lasting effect as compared to β-agonists. Clidinium bromide is the
bromide salt of clidinium. It is used for the symptomatic treatment of
peptic ulcer disease and to help relieve abdominal or stomach spasms
or cramps due to colicky abdominal pain, diverticulitis, and irritable
bowel syndrome.

Stability and Storage Conditions:

• It should be kept in a cool, dry place and stored at room temperature.
Direct sunlight is prohibited.
Type of Formulation:
• Syrup
• Tablet

Brand Name: Librax

Dicyclomine Hydrochloride

Chemical Name:

2-(Dimethylamino) ethyl bicyclohexyl-1-carboxylate HCl

Chemical Structure:

Properties and uses: It exists as a white, crystalline powder with a bitter

taste, soluble in water and chloroform. Dicyclomine HCl behaves both as an
antimuscarinic and a nonspecific antispasmodic agent. It was fi rst
introduced in 1950 and had minimized the adverse effects associated with
the atropine type of compounds. Dicyclomine has spasmolytic effect on
various smooth muscle spasms particularly those associated with the
gastrointestinal (GI) tract. It is also used in dysmenorrhoea, pylorospasm,
and biliary dysfunction.

Stability and Storage Conditions:

• It should be kept in a cool, dry place and stored at room temperature.
Direct sunlight is prohibited.

Dose: By oral or I.M. 10 to 20 mg per day in four divided doses.

Dosage forms:
Capsule: Available in 10 mg strength.
Tablet: Available in 20 mg strength.
Oral solution: Available as a 10 mg/5 mL solution.
Intramuscular injection: Available as a 20 mg/2 mL injection.

Brand Name: Bentyl, Mesbentyl