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. 17
Adrenergic agents 4
2
Adrenergic
agents 4
3
Intended learning outcomes
At the end of the lecture the students will be able to
• Categorize adrenergic blockers

• State the specific uses for the various blockers
• Outline the synthesis of Tolazoline
4
Contents
• The specific uses for the various blockers
• The synthesis of Tolazoline
5
Adrenergic blocking agents
• Adrenergic blockers are also called as antiadrenergic
drugs or sympatholytics
• Adrenergic blocking agents prevent the response of
effector organs to endogenous as well as exogenous
adrenaline and noradrenaline
• These drugs block the actions of adrenergic drugs at
alpha (α) or beta (β) adrenergic receptors
• Useful in medicine, particularly in the treatment of
cardiovascular diseases
6
Mechanism of Action of α -Adrenergic Blockers
• α -Adrenergic receptor response in clinical relevance include α1
receptor mediated contraction of arterial and venous smooth
muscle.
• α2 adrenergic receptors are involved in suppressing sympathetic
output, increasing vagal tone, facilitating platelet aggregation,
inhibiting the release of norepinephrine, and acetylcholine
• from nerve endings.
• Blockade of α1 receptors inhibits vasoconstriction induced by
endogenous catecholamines
• Vasodilatation may occur in both arteriolar resistance vessels and
veins.
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Mechanism of Action of α -Adrenergic Blockers
• α2 receptor regulates both central and peripheral sympathetic
neurons.
• Acceleration of presynaptic α2 receptors inhibits the
norepinephrine release.
• In some vascular beds, these drugs promote vasodilatation
through the release of nitric oxide (endothelial relaxing factor).
• Phenoxybenzamine inhibits the uptake of catecholamine from the
nerve terminals.
• Phentolamine and tolazoline are competitive α adrenergic
antagonists and block the receptor for 5-HT and it causes the
release of histamine from the mast cells, which is a potent
vasodilator.
8
Mechanism of Action of β-Adrenergic Receptor Blockers
• β adrenergic receptor antagonists slow the heart rate and decrease
the myocardial contractility, these prolongs the systolic conduction
and disturbs the ventricular fibres.
• Dimensions of the ventricle is decreased, oxygen consumption is
decreased, and thereby decreases the heart rate and aortic pressure.
• In blood vessels, these drugs reduces the noradrenaline release from
the sympathetic terminals and decrease the renin from kidney due to
the blockade of β receptors
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Adrenergic blocking agents: Classification
I. Alpha receptor blocking agents:

a. Beta halo alkyl amines:
i. Dibenamine
ii. Phenoxy benzamine
b. Natural and dehydrogenated ergot alkaloids:
i. Ergotamine
ii. Ergocristine
iii. Ergocriptine
iv. Ergocornine
c. Imidazole derivatives:
i.Tolazoline
ii.Phentolamine
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d. Quinazolines:
i.Prazosin
ii.Terazosin
iii.Doxazosin
e. Miscellaneous
i.Indoramine
ii.Yohimbine
iii.Chlorpromazine
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II. Beta-receptor blocking agents
a. β-Blockers with membrane stabilizing activity and intrinsic
sympathomimetic property:
i.Oxprenalol
ii.Pindalol
b. Specifi c β-blockers:
i.Timolol
ii.Nodalol
c. β-blockers with membrane stabilizing activity
i.Propranolol
d. β-blockers with cardio selective action
i. Acebutolol
ii. Atenolol
iii.Metaprolol
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Alpha adrenergic blocker: Drug Profile
Tolazoline (Synonym: Priscoline)

Chemically it is
2-benzyl-4,5-dihydro-1H-imidazole
• Tolazoline is a member of the class of imidazoles that is 4,5-dihydro-
1H-imidazole substituted by a benzyl group
Properties:It is a white, bitter taste, crystalline compound with a slight
aromatic odour, soluble in water, alcohol, and chloroform, but sparingly
soluble in ether.
Medicinal Uses:
• an alpha-adrenergic antagonist
• an antihypertensive agent and
• a vasodilator agent
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Tolazoline
It is prepared by condensation of an aminoether (obtained by

methanolysis of phenylacetonitrile) with ethylene diamine.
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Phentolamine:
• Phentolamine: Phentolamine is a synthetic imidazoline with alpha-

adrenergic antagonist activity
• Chemically it is 3-[N-(4,5-dihydro-1H-imidazol-2-ylmethyl)-4-
methylanilino]phenol
Properties: It is a white, odourless, bitter powder, soluble in water and
alcohol
Medicinal Uses:
• A nonselective alpha-adrenergic antagonist
• It is used in the treatment of hypertension and hypertensive
emergencies 15
Phenoxybenzamine (Dibenzyline)
• Phenoxybenzamine is a synthetic, dibenzamine alpha adrenergic
antagonist with antihypertensive and vasodilatory properties.
• Phenoxybenzamine non-selectively and irreversibly blocks the
postsynaptic alpha-adrenergic receptor in smooth muscle, thereby
preventing vasoconstriction, relieving vasospasms, and decreasing
peripheral resistance.
• Reflex tachycardia may occur and may be enhanced by blockade of
alpha-2 receptors which enhances norepinephrine release.
• Phenoxybenzamine is reasonably anticipated to be a human
carcinogen.
• Phenoxybenzamine is an aromatic amine.
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Properties : Colourless, crystalline compound soluble in alcohol,

water, and chloroform.
Medicinal uses:
• A major use of phenoxybezamine is in the treatment of
pheochromocytoma (tumours of the adrenal medulla)
• It is used to treat peripheral vascular diseases, suchas Raynaud’s
syndrome
• It has also been used in the case of shock and frostbite to improve
blood flow to peripheral tissues
• Used in the treatment of shock and in the treatment of pulmonary
oedema
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Prazosin: (Minipress, Prazopress)

• Prazosin is an alpha-Adrenergic Blocker. The mechanism of action of
prazosin is as an Adrenergic alpha-Antagonist.
Properties : It is a white crystalline powder, soluble in water and
alcohol. A selective α-antagonist,
Medicinal uses:
• prazosin, reduces peripheral vascular resistance and lowers arterial
blood pressure in both supine and erect patients.
• Used to treat hypertension of any degree.
• It has been used in decreasing cardiac overload
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Prazosin: (Minipress, Prazopress)
It belongs to the class of drugs known as alpha-1 blockers
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Dihydroergotamine
• Dihydroergotamine is an Ergotamine Derivative. The chemical
classification of dihydroergotamine is Ergotamines.
• Ergot alkaloids are widely used for therapy of acute migraine
headaches and include ergotamine and dihydroergotamine, both of
which act by causing vasoconstriction of the carotid artery beds.
• Ergot alkaloids have multiple side effects, but have little effect on the
liver and have not been clearly linked to instances of clinically
apparent acute liver injury.
21
Dihydroergotamine
• A 9,10alpha-dihydro derivative of ERGOTAMINE.
• It is used as a vasoconstrictor, specifically for the therapy of
MIGRAINE DISORDERS.
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Methysergide
• An ergot derivative that is a congener of LYSERGIC ACID
DIETHYLAMIDE
• It antagonizes the effects of serotonin in blood vessels and
gastrointestinal smooth muscle, but has few of the properties of
other ergot alkaloids
• Methysergide is used prophylactically in migraine and other vascular
headaches and to antagonize serotonin in the carcinoid syndrome
• Chemically it is (6aR,9R)-N-[(2S)-1-hydroxybutan-2-yl]-4,7-dimethyl-
6,6a,8,9-tetrahydroindolo[4,3-fg]quinoline-9-carboxamide is an
ergoline alkaloid.
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Methysergide
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Summary

• Mechanism action of alpha and beta adrenergic agents
• State the specific uses for the various alpha adrenergic
blockers
• Outline the synthesis of Tolazoline
25
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:

Available Formats

Course Code: BP402T

Course Title: MEDICINAL CHEMISTRY I

At the end of the lecture the students will be able to

• Categorize adrenergic blockers

• Categorize adrenergic blockers

• The specific uses for the various blockers

• The synthesis of Tolazoline

I. Alpha receptor blocking agents:

Tolazoline (Synonym: Priscoline)

It is prepared by condensation of an aminoether (obtained by

• Phentolamine: Phentolamine is a synthetic imidazoline with alpha-

Properties : Colourless, crystalline compound soluble in alcohol,

Prazosin: (Minipress, Prazopress)

Prazosin: (Minipress, Prazopress)

It belongs to the class of drugs known as alpha-1 blockers

• Categorize adrenergic blockers

The content is for educational purpose only

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