Lecture 15

Drugs affecting the immune system

Antihistaminic agents
Phuong-Thuy Thi PHAN, M.S.
 Recommended Reading
1) Beale, J.M., Block, J.H. (2011). Wilson and Gisvold’s Textbook
of Organic Medicinal and Pharmaceutical Chemistry 12th edition,
Lippincott Williams & Wilkins: Baltimore. Chapter 23. Histamine
and antihistaminic agents, p.p. 733-759.

2) Thomas L.L., David A.W. (2013). Foye’s Principle of

Chemistry 7th edition, Lippincott Williams & Wilkins: Baltimore.
Medicinal
Chapter 32. Antihistamines and related antiallergic and
antiulcer agents, p.p. 1045-1072.

3) Trương Phương, Trần Thành Đạo (2017). Hóa dược 2 (Dùng cho đào
tạo dược sĩ đại học), NXB Giáo Dục Việt Nam. Bài 50. Thuốc kháng
histamine H1, p.p. 400-416.
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 Goals
1) Different forms of histamine and receptor binding patterns and how
substitution affect agonist activity

2) The chemical classifications and SAR of H1-blockers

3) Differentiate the receptor binding patterns and structural

features needed between agonist and antagonists

4) Different approaches in getting non-CNS active and non-

sedating antihistamines

5) Important H1 blockers and the chemical principles of

their withdrawal from market
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 Histamine

L-Histidin decarboxylase

Histamin

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 Histamine receptors

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 Histamine receptors

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 Genesis O
O

Piperoxan

The initial discovery of a histamine

H
antagonist was in 1933 by Fourneau and C
O CH3 O CH3
Bovet. Most of the progress was a result N N
CH3 CH3
Ethanolamines
of isosteric modifications. This resulted in (Aminoalkyl ethers)

the classical H1 antagonists being

H
structurally very similar C
N
CH3 N
N
CH3 C N N CH3

CH3 CH3

Propylamines Ethylenediamines Piperazine

s Tricyclic
Antihistamine
s

S CH3
N Antipsychotic Tricyclic
N (Neuroleptics Antidepressants
CH3 )

Phenothiazines

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 Antihistamine H1 - General structure

A: -CH2-, -NH2, -O-, -CH2O-

n = 0, 1
X = O: ethanolamines, propanolamines
X = C: propylamines, piperidines
X = N: ethylendiamines, piperazines, phenothiazines

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 Ethylendiamines

As a class the ethylenediamines have low to moderate potency with low anticholinergic side effects, low antiemetic
effects and moderate to high sedation
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 Ethanolamines

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 Propanolamines

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 Propylamines

Contains the most potent classical H1 antagonists with low anticholinergic side effects and thus are the most widely
used

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 Reduce BBB absorption

1. Add polar or highly ionized groups.

2. Create a very high lipid soluble compound.

3. Create a zwitterion that has low ability to pass through the

BBB's
lipid barriers.

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 Piperazines (cyclizines)

They have moderate potency with a slow onset and prolong duration of action, moderate sedation and low
anticholinergic effects
They also possess peripheral and central antinausea activity, thus they are used as antiemetic, antivertigo
and antinausea products 14
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 Piperidines

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 Benzimidazole

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 Phenothiazines

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 Tricyclics

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 Tricyclics

Clarinase® = loratadin 5 mg + pseudoephedrin 60 mg x 2

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