Course Code: BP402T Course Title: Medicinal Chemistry I

Course Code: BP402T
Course Title: MEDICINAL CHEMISTRY I
Course Leader:
Mrs. M. K. Yuvapriya (yuvapriya.py.ph@msruas.ac.in)
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Faculty of Pharmacy ©M. S. Ramaiah University of Applied Sciences
Lecture No. 16
Adrenergic agents 3
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Adrenergic
agents 3
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Intended learning outcomes
By the end of the lecture student will be able to
• General classification of Adrenergic agents

• Propose the specific uses for the various classes of
Adrenergic agents
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Sympathomimetic agents-Classification
• Adrenergic agents are divided into three classes
I. Direct-acting adrenergic agonists
• They bind to and activate α1, α2, β1, and β2 receptors
• Naturally occurring molecules, which bind to these receptors include
NE (a neurotransmitter which binds to α1, α2, and β1 receptors),
Epinephrine (a hormone produced in and secreted from the adrenal
medulla, which binds to α1, α2, β1, and β2 receptors, it is a
nonselective adrenergic agonists), and Dopamine (also a
neurotransmitter, which binds to α1, α2, and β1receptors).
Examples of drugs: xylometazoline, phenylephrine, methoxamine.
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II. Indirect-acting adrenergic agonists

• They produce NE-like actions by stimulating NE release
and preventing its reuptake and produces activation.
Example: Tyramine.
III. Dual-acting adrenergic agonists
• These agents act as direct and indirect adrenergic agonists
(hence, dual-acting).
• They bind to adrenergic receptors and stimulate NE
release
Examples: Ephedrine, Amphetamine, Mephenteramine.
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Classifications Based on Therapeutic Uses
• Adrenergic drugs used for raising blood pressure (vaso-constrictors):
Noradrenaline, Metaraminol
• Drugs used for their ionotropic action on the heart: Dopamine,
Dobutamine, Xamoterol
• Drugs used as central stimulants: Amphetamine (Benzedrine)
• Drugs used as smooth muscle relaxants: Adrenaline (epinephrine),
Isoprenaline, Isoxsuprine
• Selective β2 stimulant: Salbutamol
• Drugs used in allergic reactions: Adrenaline, Ephedrine
• Drugs used as local vaso-constrictors: Adrenaline, Phenylephrine,
Naphazoline
• Drugs used for suppressing the appetite: Fenfl uramine,
Phenteramine, Amphetamine
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Classification Based on Chemical Structures
I. Catecholamines
Compounds with hydroxyl (–OH) substitution in the third and fourth
position of the benzene ring are termed as catecholamines.
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II. Noncatecholamines
• Those compounds that lack the hydroxyl at third and fourth position
of the benzene ring are noncatecholamines.
• They release noradrenaline or dopamine from the sympathetic
neurons.
• This indirect action produces effects mainly resembling those of
externally administered noradrenaline.
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II. Noncatecholamines contd: Examples:
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Sympathomimetic agents: Drug profile
Noradrenaline (Synonym: Norepinephrine, Nephridine)
• These are the drugs which directly acts to adrenergic receptors and
stimulates sympathetic action
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Noradrenaline (Synonym: Norepinephrine, Nephridine)
• Properties : It is a white or brownish-white, crystalline powder, slightly
soluble in ethanol and soluble in water. It differs from adrenaline only
by lacking the methyl substitution on the amino ethanol.
• L-isomer is pharmacologically active.
Medicinal uses :
• Noradrenaline is a potent agonist for α1 receptors and has relative
actions on β2 receptors.
• It is used as a vasoconstrictor in some local anaesthetic solutions for
dental use.
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Adrenaline (Synonym: Epinephrine)
• Adrenaline is a catecholamine and belongs to the family of biogenic
amines
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Adrenaline (Synonym: Epinephrine)
Properties:
• It is a white or creamy white, sphaero-crystalline powder. It dissolves in
solutions of mineral acids, potassium hydroxide, and of sodium hydroxide,
but sparingly soluble in water, insoluble in ethanol and ether.
Medicinal Uses:
• It is used as a sympathomimetic, broncholytic, and antiasthmatic.
• It is used to prevent bleeding during surgery or in case of inner organ
bleeding. Because adrenaline leads to constriction of blood vessel, it is
administered in combination with local anaesthetics. In this combination,
anaesthetics have long-lasting effect and can be administered in smaller
doses.
• It is used in the treatment of heart block or circulatory collapse and open-
angle glaucoma.
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Sympathomimetic agents: Direct acting
Phenylephrine:
1-(3-hydroxyphenyl)-2-methylaminoethanol
• Phenylephrine differs from adrenaline only by lacking the 4-OH

group on the benzene ring
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Synthesis of Phenylephrine:
Phenylephrine is prepared by condensation of 3-chloroacetylphenol
with methylamine followed by catalytic reduction.
Properties: Phenylephrine is available as hydrochloride salt. It is white,

odorless, bitter taste, crystalline powder. It is soluble in water, alcohol,
and glycerol. It should be stored in airtight container to protect from
light because it is decomposed by light.
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Phenylephrine:
Medicinal Uses.
• Phenylephrine is a selective α1-receptor agonist
• Oral absorption is not reliable and so it is given parenterally or
topically as eye or nasal drops
• Phenylephrine predominantly acts on peripheral arterioles results
in a rise in systolic and diastolic pressures accompanied by a
marked reflex bradycardia
• Phenylephrine is used as a nasal decongestant, mydriatric and as a
vasopressor agent
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Dopamine (Domin, Dopacard):
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Dopamine (Domin, Dopacard):

Properties : It is a white or almost white crystalline powder, soluble in
alcohol, sparingly solublein acetone and methylene chloride, but
freely soluble in water. It is used in the treatment of shock.
Medicinal uses:
• It works by improving the pumping strength of the heart and
improves blood flow to the kidneys
• Dopamine injection (Intropin) is used to treat certain conditions
that occur when you are in shock, which may be caused by heart
attack, trauma, surgery, heart failure, kidney failure, and other
serious medical conditions
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Methyldopa:
• The L-isomer of alpha-methyldopa, is levo-3-(3,4-
dihydroxyphenyl)-2-methylalanine
• Methyldopa is a white to yellowish white, odorless fine powder,
and is soluble in water.
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Methyldopa:
• It is an α 2 adrenergic receptor agonist acts centrally by decreasing
the sympathetic outflow which in turn lowers blood pressure
Medicinal uses:
• To treat hypertension in combination with diuretics
• To treat pregnancy-induced hypertension
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N-(2,6-dichlorophenyl)-4,5-dihydro-1H-
imidazol-2-amine
Clonidine:
• Clonidine, an imidazoline-derivative hypotensive agent is a centrally-
acting α2-adrenergic agonist thereby reducing sympathetic outflow
and noradrenaline release
• It crosses the blood-brain barrier and acts in the hypothalamus to
induce a decrease in blood pressure.
Medicinal uses:
• In moderate to severe hypertension
• For withdrawal therapy of alcohol opioids
• To diagnose pheochromocytoma ( is a neuroendocrine tumor of the
medulla of the adrenal glands) 22
Dobutamine: (Cardiject, Dotamin, Kardia)
Dobutamine is a synthetic catecholamine derivative
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Dobutamine: (Cardiject, Dotamin, Kardia)
• Dobutamine is a racemic mixture of two enantiomeric forms
• The (+) isomer has potent β-agonistic actions.
• The (–) isomer has potent α1-agonistic and poor β-agonistic actions
Properties : It is a white or almost white crystalline powder, sparingly
soluble in water and alcohol, and soluble in methanol.
Medicinal uses:
• Dobutamine is used in patients of heart failure associated with
myocardial infarction, open heart surgery and cardiomyopathy
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Isoproterenol: Synonym: Isoprenaline, Isoprim, Isosol,
Neo-Epinin
• It is a non-selective β adrenoreceptor agonist that is the
isopropylamine analog of epinephrine (adrenaline)
It is a synthetic Isopropyl analogue of adrenaline
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Isoproterenol:
Properties : It is a white or almost white crystalline powder, freely
soluble in water, sparingly soluble in alcohol, practically insoluble in
methylene chloride.
Medicinal uses:
• Its primary use is in the treatment of bronchial asthma
• It is used as an antiarrhythmic agent and
• The treatment of shock to increase heart rate
• used as a bronchodilator.
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Terbutaline: an ethanolamine derivative, is a β2 adrenergic
receptor agonist
N-tert-butyl-N-[2-(3,5-dihydroxyphenyl)-2-hydroxymethyl] amine
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Terbutaline:
Properties:
• Terbutaline is a white, odorless, bitter taste crystalline powder. It is
soluble in water, slightly soluble in alcohol and practically insoluble
in ether and chloroform. It should be protected from tight
• Available as its sulphate salt
Medicinal Uses:
• used to prevent and treat wheezing, shortness of breath, and
chest tightness caused by asthma, chronic bronchitis
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Salbutamol:(Synonym: Albuterol, Asthalin, Salbid)
A short-acting beta-2 adrenergic agonist that is primarily used as a
bronchodilator agent to treat ASTHMA
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Salbutamol:(Synonym: Albuterol, Asthalin, Salbid)
Properties : It is a white or almost white crystalline powder, sparingly
soluble in water, but freely soluble in ethanol.
Medicinal uses :
• It has strong β2 adrenergic activity
• It is useful in the treatment of acute myocardial infarction, severe left
ventricular failure
• It has been used to arrest premature labour and is effective in ocular
hypotension by topical application
• It is used only as a bronchodilator and is the drug of choice in the
treatment of bronchial asthma
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Salbutamol Synthesis:
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Bitolterol:
[4-[2-(tert-butylamino)-1-hydroxyethyl]-2-(4-methylbenzoyl)oxyphenyl]4-methylbenzoate
• Bitolterol is the di-4-toluate ester of (+-)-N-tert-butyl noradrenaline

(colterol).
• A pro-drug for colterol, a beta2-adrenergic receptor agonist,
bitolterol is used as its methanesulfonate salt for relief of
bronchospasm in conditions such as asthma, chronic bronchitis and
emphysema
• It has a role as a bronchodilator agent, an anti-asthmatic drug, a
beta-adrenergic agonist and a prodrug.
• It is a member of ethanolamines, a carboxylic ester, a diester, a
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secondary amino compound and a secondary alcohol.
Naphazoline (Ocucel Eye Dropa):

• Naphazoline is an imidazole derivative and a direct-acting
sympathomimetic amine with vasoconstrictive activity.
• Upon ocular administration, naphazoline exerts its effect by acting
on alpha-adrenergic receptors in the arterioles of the conjunctiva to
produce vasoconstriction, resulting in decreased conjunctival
congestion and diminished itching, irritation and redness
• It is used topically as nasal decongestant
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6-tert-butyl-3-(4,5-dihydro-1H-imidazol-2-ylmethyl)-
2,4-dimethylphenol;hydrochloride
Oxymetazoline: imidazole derivative
• A direct acting sympathomimetic used as a vasoconstrictor to
relieve nasal congestion
• An imidazole derivative with a direct acting sympathomimetic
property
• It binds to and activates alpha-2 adrenergic receptors and
congestion
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Oxymetazoline:
Medicinal uses:
• This medication is used for temporary relief of congestion in the nose
caused by various conditions including the common cold, sinusitis, hay
fever, and allergies.
• It works by narrowing the blood vessels in the nose area, reducing
swelling
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Xylometazoline (Synonym: Otrivin, Otrinoz, Decon)
• imidazole derivative/ an alkylbenzene
2-(4-tert-butyl)2, 6-dimethylbenzyl)-2-
imidazoline.
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Xylometazoline:
• A nasal vasoconstricting decongestant drug which acts by binding to
the same receptors as adrenaline.
• It is applied as a spray or as drops into the nose to ease inflammation
and congestion of the nasal passageways.
• It binds alpha-adrenergic receptors to activate the adrenal system
which causes systemic vasoconstriction, thereby easing nasal
congestion.
Medicinal uses:
Xylometazoline nasal (for use in the nose) is used to treat stuffy nose
caused by allergies, sinus irritation, or the common cold
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Summary
• Adrenergic drugs are also called sympatho-mimetic drugs.

• They work out by stimulating the sympathetic nervous
system
• They act directly or indirectly or by mixed actions
• Drug profile of some direct acting sympatho-mimetic
drugs
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Disclaimer
• Some of the contents of this subject has been sourced from web
sources and e-books.
• REFERENCES -
– www.google.com
– en.wikipedia.org
The content is for educational purpose only
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THANK YOU
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Course Code: BP402T Course Title: Medicinal Chemistry I

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Course Code: BP402T Course Title: Medicinal Chemistry I

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Copyright:

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Course Code: BP402T

Course Title: MEDICINAL CHEMISTRY I

By the end of the lecture student will be able to

• General classification of Adrenergic agents

II. Indirect-acting adrenergic agonists

• Phenylephrine differs from adrenaline only by lacking the 4-OH

Properties: Phenylephrine is available as hydrochloride salt. It is white,

Dopamine (Domin, Dopacard):

It is a synthetic Isopropyl analogue of adrenaline

• Bitolterol is the di-4-toluate ester of (+-)-N-tert-butyl noradrenaline

Naphazoline (Ocucel Eye Dropa):

• Adrenergic drugs are also called sympatho-mimetic drugs.

The content is for educational purpose only

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