Antihistaminics

Histamine

• physiologically active amine C5H9N3

• plant and animal tissue• Released from mast cells as part of an allergic

reaction (IgE / PG / LT / TNF-A / SP/ NKA Complement-mediated)

-Gastric Secretion-Capillary Dilatation-Bronchoconstriction-Hypotension Imidazoline

ring and amine gp

Synthesis

• Decarboxylation of AA Histidine by Histidine decarboxylase

• Mast cells and basophils

Mechanism of Action

• Combining with specific cellular receptors on cells viz H1-H4 ; Leucocyte diapedesis Neutrophil Chemotaxis Mast Cell Degranulation

• Primarily H1-mediated in Lewis’ Triple Response / UV

• H2-H4 blockers / Atypical Antihistaminics found largely ineffective

Type Location Function

H1 Found on smooth muscles, endothelium, and central nervous system tissue

Causes vasodilation, bronchoconstriction bronchial smooth muscle contraction, separation of endothelial cells (responsible for hives), and pain and itching due to insect stings; the primary receptors involved in allergic rhinitis symptoms and motion sickness; sleep regulation.

H2 Located on parietal cells Primarily stimulate gastric acid secretionAnd we use antiacidic drugs for this receptor

H3 Found on central nervous system and to a lesser extent peripheral nervous system tissue

Decreased neurotransmitter release: histamine, acetylcholine, norepinephrine, serotonin

H4 Found primarily in the basophils and in the bone marrow. It is also found onthymus, small intestine, spleen, andcolon.

Plays a role in chemotaxis.

1st Antihistaminic

• Piperoxan

• Discovered in 1933 by Jeff Forneau and Daniel Bovent while developing a guinea pig animal model of anaphylaxis

• They received the Nobel Prize in 1957

Antihistaminics

• Pharmaceutical agents that inhibit the action of histamine

• blocking its attachment to histamine receptors (Classic Antihistaminics)

• inhibiting the enzymatic activity of histidine decarboxylase (atypical antihistaminics)

• The term antihistamine only refers to H1 receptor antagonists

ClassificationH1 Blockers

Traditional Sedatives (esrt 1st Gen <1981)Low-Sedation agents (erst 2nd Gen)

H2 / H3 / H4-receptor Antagonists

Tricyclic Antihistaminics

Histidine Decarboxylase Enzyme-Inhibitors

Mast Cell Degranulation Inhibitors

• a

Traditional Sedative H1 blockers

• a

Low-Sedation H1 Blockers

• aa

H2 Receptor Antagonists

• Parietal Cells – Inhibit Gastric Secretion

• Cimetidine• Ranitidine• Nizatidine• Roxatidine• Famotidine• Lafutidine

H3 Receptor Antagonists

• Nootropics / Neuromodulators

• Ciproxifan• Clobenpropit• Conessine

H4 Receptor Antagonists

• Immunomodulators

• Thioperamide• VUF-6002• JNJ 7777120

Histidine Decarboxylase Inhibitors

• Tritoqualine• Catechin

Mast Cell Degranulation Inhibitors

• Sodium Cromogylcate• Nedocromil

• Inhalational Agents ; Ineffective in Cutaneous Dermatoses

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