2. Introduction:
Autacoids are biological factors (molecules) which like local hormones:
• Short half life/ brief duration of action
• Act near their site of synthesis
• Endogenous compounds
• Involved in physiological and pathological processes
4. Functions
They take part in:
1. Inflammation
2. Allergic reactions
3. Anaphylactic reactions( not so much)
4. Neurotransmission
5. Gastric acid secretion
5. In the central nervous system, they are responsible for
1. Wakefulness
2. Decreased Appetite
3. Regulation of drinking
4. Regulation of temperature
5. Control of blood pressure
6. Perception of pain
6. Histamine
• Histamine is an inflammatory biological amine
• Histamine is a β-imidazolylethylamine derivative present in all
mammalian tissues.
• It was first discovered by SIR HENRY DALE.
• Its synthesis occurs in mast cells, parietal cells of gastric mucosa,
CNS, periphery.
• It has an important role in the regulation of gastric acid secretion.
7. Biosynthesis of Histamine
• Histamine is synthesized in cytoplasmic granules of its storage cells,
mast cells & basophils.
• It is formed from naturally occurring amino acid, L-histidine, via the
catalysis of the phosphate – dependent enzyme histidine
decarboxylase
• Inhibitors of histidine decarboxylase
• α-fluoromethyl histidine
• Certain flavonoids
10. Metabolism of Histamine
• Takes place by the enzymatic inactivation.
• Enzymes that involve in the metabolism are:
1. Histamine N-methyl transferase(HMT)
2. Diamine oxidase.
• Histamine is metabolized to N- methylimidazole acetate and
imidazole acetate.
• Both are excreted through urine
11.
12. Sites of Histamine release
1. Mast cell site: Pulmonary tissue (mucosa of bronchial tree)
• Skin
• GIT(intestinal mucosa)
• Conc. Of histamine is particularly high in these tissues
2. Non-mast cell sites:
• CNS (neurons)
• Epidermis of skin.
• GIT(gastric cells)
• Cells in regenerating or rapidly growing tissues
• Basophils (in the blood)
14. Importance of Histamine
• It is not used therapeutically but in the past it has been used to test
acid secreting capacity of stomach.
• To test bronchial hyperactivity in asthmatics.
15. Receptors
• Histamine receptors are belonging to the family of G-Protein coupled
receptors.
• The sub types of histamine receptors are:
• H1
• H2
• H3
• H4
16. H1 H2 H3 H4
Distribution SM(intestine,
bronchi), blood
vessels
Gastric parietal
cells, blood
vessels, heart
Brain
presynaptic,
lung ,spleen,
blood vessels
Eosinophils,ne
utrophils, CD4
cells
Function Contraction of
SM,
Vasodilatation,
pain
mediation,
increased
permeability
Acid secretion,
vasodilation,
force of
contraction,ca
pillary
permeability
Decrease
histamine and
norepinephrin
e, gastric
secretion,
vasodilation
Chemotaxisof
WBC,
antagonists Chlorpheniram
ine, cetrizine
Cimetidine,fam
otidine
thioperamide Thioperamide
Agonist histaprodifen dimaprit imetit imetit
17. Histamine pharmacology: from Sir Henry Dale to the 21st century
British J Pharmacology, Volume: 177, Issue: 3, Pages: 469-489, First published: 19 October 2018, DOI: (10.1111/bph.14524)
18.
19. • H2 receptors are a potent stimulant of cAMP production and
increases intracellular Ca2+ concentrations and releases Ca2+ from
the intracellular stores
• cAMP, cyclic is a second messenger important in many biological
processes.
• cAMP is a used for intracellular signal transduction in many different
organisms.
20. Histamine Antagonists:
• Histamine antagonist block the action of histamine at H1,H2,H3,H4
receptors
• Antihistamine is a drugs that combat the histamine released during
an allergic reaction by blocking the action of the histamine on the
tissue.
• The term antihistamine only refer to H1 receptor antagonist.
21.
22. Therapeutic uses of antihistamine
1. Allergic condition
2. Common colds
3. Motion sickness
4. Vertigo
5. Pre anesthetic medication
6. Cough
7. Parkinsonism
8. Acute muscle dystonia
24. H3 antagonist
• Reduce acetylcholine serotonin and nor epinephrine
• Ciproxifan
• Clobenpropit
• thioperamide
25. Mast Cell Stabilizers
• inhibit the release of allergic mediators from mast cells
• are used clinically to prevent allergic reactions to common allergens.
disodium cromoglycate, ketotifen
• preventative treatment of bronchial asthma
• allergic conjunctivitis
• vernal keratoconjunctivitis
Overview of the main functions of the histamine receptors. Histamine is formed in various cell types (rectangular box) and orchestrates numerous actions via binding to four receptor types, designated as H1–H4. Gas, Gai/o, Gaq/11: G protein Ga subunits.
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