Classification of Histamine

  • Classification of Histamine: Based on receptor types—H1, H2, H3, and H4
  • Classification of Histamine: Involved in allergy, gastric acid, CNS, and immunity.
  • Histamine is a biogenic amine derived from the decarboxylation of the amino acid histidine.
  • It plays pivotal roles in immune responses, gastric acid secretion, and as a neurotransmitter.

Structure of Histamine

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Synthesis:

  • From the amino acid histidine by the enzyme histidine decarboxylase.

Storage:

  • Primarily stored in mast cells (in tissues) and basophils (in blood). Also found in the brain as a neurotransmitter.
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Release Triggers:

  • Allergic reactions (type I hypersensitivity reactions).
  • Tissue injury or mechanical trauma.
  • Certain drugs and chemicals.

Functions of Histamine:

  • Immune Response: Mediates inflammation and allergic reactions by increasing vascular permeability and attracting immune cells.
  • Gastric Secretion: Stimulates parietal cells in the stomach to produce hydrochloric acid.
  • Neurotransmission: Involved in wakefulness and cognitive functions.
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Histamine Receptors:

  • Histamine exerts its effects through four types of receptors, designated H1 to H4, each with distinct locations and functions.

Classification of Histamine1

  1. H1 Receptors:

    • Location: Smooth muscles, endothelium, central nervous system.
    • Functions: Mediate allergic symptoms (e.g., vasodilation, bronchoconstriction), contribute to wakefulness.
  2. H2 Receptors:

    • Location: Parietal cells of the stomach, heart.
    • Functions: Stimulate gastric acid secretion, regulate heart rate.
  3. H3 Receptors:

  4. H4 Receptors:

    • Location: Bone marrow and white blood cells.
    • Functions: Involved in immune cell chemotaxis and activation.
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Pharmacological Effects of Histamine

  • Vasodilation, particularly of small vessels → decreases blood pressure.
  • Increased capillary permeability → edema and urticaria.
  • Smooth muscle contraction → bronchoconstriction (H1 effect).
  • Gastric acid secretion (H2 effect).

Histamine Antagonists

Histamine Antagonists

  1. H1 Antagonists (H1 Blockers):

    • Purpose: Primarily used to treat allergic reactions, such as hay fever, urticaria, and allergic conjunctivitis.
    • Examples: Diphenhydramine, cetirizine, loratadine.
    • Mechanism: Block H1 receptors to reduce vasodilation, capillary permeability, and smooth muscle contraction associated with allergic responses.
  2. H2 Antagonists (H2 Blockers):

    • Purpose: Used to reduce gastric acid secretion in conditions like peptic ulcers and gastroesophageal reflux disease (GERD).
    • Examples: Ranitidine (withdrawn in many markets due to safety concerns), famotidine, cimetidine.
    • Mechanism: Block H2 receptors on parietal cells, decreasing the production of stomach acid.
  3. H3 and H4 Antagonists:

    • Current Status: Primarily under research; potential applications in neurological disorders and immune modulation.
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Below is a concise table summarizing the four histamine receptor subtypes.

Receptor Location Signaling Pathway Key Effects (Actions) Example Drug (Typically an Antagonist)
H1 Smooth muscle (bronchi, gut), endothelium, brain Gq → ↑ IP3, DAG – Bronchoconstriction
– Vasodilation (via NO release)
– ↑ Vascular permeability
– Itching, pain (nerve endings)
Diphenhydramine (1st-gen H1 blocker)
H2 Gastric parietal cells, heart, mast cells, brain Gs → ↑ cAMP – ↑ Gastric acid secretion
– Positive inotropic & chronotropic effects on the heart
Ranitidine (H2 blocker)
H3 Presynaptic nerve terminals (mainly in the CNS) Gi → ↓ cAMP – Inhibition of histamine release (auto-receptor)
– Modulation of neurotransmitter release
Pitolisant (H3 inverse agonist/antagonist)
H4 Hematopoietic cells (eosinophils, T cells, mast cells) Gi → ↓ cAMP – Chemotaxis & inflammation
– Role in immune cell activation
Still under research (no major drug in use)

Note:

  • H1 antagonists (antihistamines) are often used for allergic conditions, motion sickness, etc.
  • H2 antagonists are used for peptic ulcers and acid reflux (GERD).
  • H3 antagonists/inverse agonists have emerging roles in sleep-wake regulation (e.g., Pitolisant for narcolepsy).
  • H4 antagonists are still in experimental stages, mainly targeting inflammatory and immune disorders.
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