Histamine is an important chemical messenger that mediates allergic and inflammatory responses. It is synthesized from the amino acid histidine and stored in mast cells. Upon release, histamine binds to four types of histamine receptors (H1-H4) to produce various effects throughout the body, such as gastric acid secretion and smooth muscle contraction. Antihistamines are commonly used to treat allergic reactions by blocking H1 receptors, while H2 receptor antagonists inhibit gastric acid production. Histamine plays a key role in many physiological processes and understanding its receptors has led to treatments for conditions like ulcers, allergies, and inflammation.

1. Presentation on
Histamine
Presented by: Presented to:
Rabiya Ahsan Dr. Badruddin
(research scholar) associate professor(Jr.)
Integral University Lucknow
2020-2021

2. Introduction
• First Autacoid to be discovered. (Greek: autos=self; akos=cure)
• Synthesized in 1907
• Isolated and demonstrated to be a natural constituent of mammalian
tissues (1927); hence the name Histos=Tissue
• H1 was discovered in1966
• H2 in1972
• H3 in1987
• H4 in 2001
Definition:-Chemical messenger that mediates a wide range of cellular
responses, including allergic and inflammatory reactions, gastric acid
secretion, and neurotransmission in parts of the brain. Plays an important
role in gastric acid secretion.

3. Synthesis, storage and release
Synthesized by decarboxylation of amino acid histidine.
Histamine is present in storage granules of mast cells & also found in
skin, lungs, liver, gastric mucosa etc.
Histamine is released by several mechanism.
• Immunological release
• Chemical and mechanical release
• Loss of granules from mast cells also release histamine since sodium
ions in the extracellular fluids rapidly displace histamine from the
complex.

4. Mechanism of histamine
Histamine
H1 Receptor H2 Receptor H3 Receptor
Increase Ca2+ Decreased
cAMP
increased
cAMP
• Smooth muscle contraction.
• Increased capillary.
• Permeability.
• Vasodilation.
• Sensory nerve ending pain &
itching
• Increased gastric acid secretion
• Blood vessels
• Vasodilation
• Increased capillary
• permeability
• Decreased histamine
release
• Decreased secretion
• vasodilation

5. HISTAMINE (Pharmacological Effects/ biological
function)
1. Cardiovascular system. vasodilation
2. Smooth muscle of bronchioles; contraction of nonvascular smooth
muscle.
3. Peripheral Nervous system: itching and pain
4. Exocrine Glands
5. Gastric glands
6. Salivary glands
7. Sweat glands Secretion
8. Pancreas
9. Bronchial glands
10. Lacrimal glands
secretion

6. Histamine action through its receptors
Types Location Effect Treatment
H1 Throughout body (smooth
muscles, heart, CNS)
Bronchoconstriction,
vasodilation, pain, motion
sickness
Allergies, nausea, sleep
disorder
H2 Specific location in the
body (gastric parietal cell,
vascular smooth muscle,
CNS, heart, uterus
Regulate gastric acid
secretion, vasodilators
Stomach ulcers
H3 CNS, small intestine Neural presynaptic
receptor, may function to
release histamine
unknown
H4 Spleen, thymus,
leukocytes
Mast cell chemotaxis Treatment of
autoimmune diseases like
rheumatoid arthritis

7. Anti-histaminic agents
• Anti-histaminic agents usually referred to those opposing the H1
mediated effects of histamine.
These are classified as:
• First generation
• Second generation
• Those opposing the H2 mediated effect of histamine are known as
anti-secretory agents.

8. H1-RECEPTOR ANTAGONISTS (Conventional Antihistaminics)
First generation Antihistaminics
Highly sedative:
• Diphenhydramine
• Dimenhydrinate
• Promethazine
• Hydroxyzine
Moderately sedative:
• Pheniramine
• Cyproheptadine
• Meclizine
• Buclizine
• Cinnarazine
Mild sedative: Chlorpheniramine, Dexchlorpheniramine, Dimethindene,
Triprolidine, Mebhydroline, Cyclizine, Clemastine

9. Uses:
• Adjunctive in anaphylaxis and other cases where histamine release
can occur.
• Antiallergy
• Prevent motion sickness/antiemetic
• Antitussive
ADR
• Sedation, dizziness, fatigue and antimuscranic effects (dry mouth,
constipation, urinary retention, blurred vision)

10. • Second generation Antihistaminics: Fexofenadine, Loratadine,
Desloratadine, Cetrizine, Levocetrizine, Azelastine, Mizolastine,
Ebastine, Rupatadine.
Uses:
• Pruritus, allergic rhinitis, urticaria
ADR
• Fatigue, dry mouth, pharyngitis, dizziness and arrhythmia

11. H2 antihistaminics
• Cimetidine
• Ranitidine
• Famotidine
• Roxatidine
• Primarily used in peptic ulcer and other gastric hypersecretory states
H3 antihistaminics: Thioperamide
No clinical utility.
Mast cell stabilisers (histamine release inhibitors)
Cromolyn and nedocromil.
Dual acting antihistamines (H1 antihistaminic action + mast cell stabilisers)
Azelastine and kitotifen.

12. Treatment of peptic ulcers/other gastric conditions
Peptic ulcer disease causes can be
• Hypersecretion of acid and pepsin
• Infection due to helicobacter pylori
Other risk factors
• NSAID’s like aspirin, ibuprofen etc
• Cigarette smoking, alcohol consumption, oily and spicy diet
• Emotional stress
Treatment includes
Antacids: aluminium and magnesium hydroxide, NaHCO3

13. • H2 histamine receptor antagonist- ranitidine
• Protective mucosal barriers- sucralfate, carbenoxolone
• PPIs- omeparazole, pantoparazole
• Prostaglandins-misoprostol
• Muscarinic antagonists- pirenzipine
• Along with antibiotics- if infection with H- pylori

14. Reference
• JOHN H.BLOCK & JOHN M WILSON& GISVOLD’S Organic Medicinal &
Pharmaceutical chemistry. (Pg): 698 – 728
• D.SRIRAM & P.YOGEESWARI -Medicinal chemistry. (Pg): 278 – 302
• BERTRAM G.KATZUNG, SUSAN B.MARTERS ANTHONY J.TREVOR Basic
& Clinical pharmacology (Pg) : 277
• K.D TRIPATHI Essentials of medical pharmacology. (Pg): 159 – 160.