Medicinal Chemistry

1. Histamine
 Histamine :- Histamine: A substance that plays a major
role in many allergic reactions, dilating blood vessels
and making the vessel walls abnormally permeable.
Histamine is part of the body's natural allergic response to
substances such as pollens.
 Functions of Histamines:-
Histamine is a signaling molecule, sending messages
between cells. It tells stomach cells to make
stomach acid and it helps our brain stay awake. Some
antihistamines can make us sleepy and other
antihistamines are used to treat acid reflux.

2. Histamine

3. Formation of Histamine in Body

4. Histamine
 English scientists George Barger and Henry H. Dale
first isolated histamine from the plant fungus ergot in
1910, and in 1911 they isolated the substance from animal
tissues.
 It is formed by the decarboxylation (the removal of a
carboxyl group) of the amino acid histidine.

5. Histamine Receptors and Their
Distribution
 Almost all mammalian tissues contains histamine.
 Widely distributed in skin, GIT, mucosa, lungs, brain and
bone- merrow .
 It is also component of some venoms, Sting secreation,
bacteria and plants .
 The mast cell is predominant storage site for histamine in
most tissues.
 The concentration of histamine is particularly high in
tissue that contain large members of most cells such as
skin , bronchial tree mucosa and intestinal mucosa.

6. HISTAMINE AND ITS
RECEPTORS
 H1 – Smooth muscle, endothelium, CNS.- Bronchoconstriction,
vasodilation, separation of endothelial cells, pain and itching, allergic
rhinitis, motion sickness.
 H2 – gastric parietal cell, basophils. Regulate gastric acid secretion,
inhibition of IgE-dependent degranulation.
 H3 - CNS cells, and some in peripheral NS. Presynaptic, feedback
inhibition of histamine synthesis and release. They also control
release of DA, GABA, ACh, 5-HT & NE.
 H4 - Highly expressed in bone morrow and white blood cells.
Mediate mast cell chemotaxis..

7. Classification of Hisatamine

9. H2 Receptor Antagonists
 :- are a group of medicines that reduce the amount of acid
produced by the cells in the lining of the stomach are
commonly called H2 blockers.
 Cimetidine ( Tagamet)
 Ranitidine ( Zantac)
 Famotidine (Pepcid , Pepcid AC) - Nizatidine ( Axid)
These products have been approved for the relief of “heartburn
associated with acid indigestion, and sour stomach.” They
should not be taken for longer than 2 weeks and are not
recommended for children < 12 years of age.

10. MOA of H2 blockers
 The H2 antagonists are competitive antagonists of histamine at
parietal cell
 H2 receptor .They suppress the normal secretion of acid by parietal
cells and the meal –stimulated secretion of acid .
 They accomplish this by two mechanism : Histamine released by
ECL(enterochromaffin – like) cells in the stomach is blocked from
binding on parietal cell H2 receptor , which stimulate acid secretion :
therefore other substances that promote acid secretion ( such as
gastrin and acetylcholine ) have a reduce effect on parietal cell when
the H2 receptors are blocked

11. Side effects of H2 blockers
 Some of the side effects that may occur with H2 receptor
blockers include:
 constipation
 diarrhea
 difficulty sleeping
 dry mouth
 dry skin
 headaches
 ringing in the ears
 a runny nose
 trouble urinating

12.  The H2-receptor antagonists were the result of the international
modification of the histamine structure and deliberate search for a
chemically related substance that would act as competitive inhibitor
of the H2-receptors.

14. Drugs of H2 Receptor Antagonists

15. When to Use H2 Receptor Antagonists
 To reduce acid reflux which may cause heartburn or inflammation of
the gullet (esophagitis). These conditions are sometimes called
gastroesophageal reflux disease (GERD).
 To treat ulcers in the stomach and in part of the gut (the duodenum).
 To help heal ulcers associated with anti-inflammatory agents
(NSAIDs).
 In other conditions where it is helpful to reduce acid in the stomach.
 Also :Damage to the stomach and/or intestines due to stress or
 trauma,
 -Pancreatic problems
 Stomach or intestinal ulcers (sores) resulting from damage caused by
medication used to treat rheumatoid arthritis.

16. How H. Pylori causes ulcer?
• This bacteria burrows through the protective 1mm
thick mucus layer and attaches itself to the epithelial of
stomach walls to avoid acidic conditions. Furthermore
it also produces large amounts of urease, which breaks
down the urea present in the stomach to carbon
dioxide and ammonia. The ammonia protects it from
stomach acidity and is toxic to epithelial cells which
secrete mucus. It also produces cell damaging
chemicals such as proteases and vacuolating cytotoxin
A (VacA). All together the mucus barrier is damaged
and made thinner than 0.5 mm and in this state the
stomach becomes more susceptible to attack by acid
and pepsin

18. Ranitidine
Structure:
IUPAC:[1-({2-[({5-[(dimethylamino)methyl]furan}methyl)sulfanyl]
ethyl}amino)-2-nitroethenyl](methyl)amine
Properties:
white to pale yellow, granular substance, Characteristic odour, Bitter
taste, Water soluble, sensitive to light and moisture.
16
Molecular formula: C13H23N4O3S

20. Sucralfate
medication used to treat stomach
ulcers, gastroesophageal reflux disease (GERD), radiation
proctitis, and stomach inflammation and to prevent stress
ulcers