Chapter 11: Histamine and Antihistaminics

Histamine Overview

• Histamine is a "tissue amine" predominantly found in animal tissues and certain plants, notably stinging nettle.
• Initially studied by Dale in the early 20th century, it is linked to allergic reactions and hypersensitivity phenomena.
• Plays crucial physiological roles and is largely concentrated in mast cells, particularly in:
  • Skin
  • Gastric and intestinal mucosa
  • Lungs
  • Liver
  • Placenta
• Non-mast cell histamine exists in the brain, epidermis, gastric mucosa, and growing regions.
• Turnover rate of mast cell histamine is slow while non-mast cell histamine has a rapid turnover.

Synthesis, Storage, and Destruction

• Biochemically known as β imidazolylethylamine, histamine is synthesized from the amino acid histidine and is rapidly degraded via oxidation and methylation.
• Within mast cells, histamine is stored in granules, bound to an acidic protein and heparin; exocytosis releases histamine into the extracellular fluid.
• Histamine is inactivated when taken orally due to absorption and degradation by the liver.

Histamine Receptors

• Four histaminergic receptors have been classified: H₁, H₂, H₃, and H₄.
• H₁ and H₂ receptors were first identified, with H₁ being specifically blocked by early antihistamines.
• The first H₁ antagonist, burimamide, was developed by Sir James Black in 1972.
• H₃ receptor, identified in 1983, acts primarily as an autoreceptor in the brain, modulating the release of histamine, yet lacks significant clinical applicability.
• The H₄ receptor, discovered in 2001, shares significant homology with the H₁ receptor and binds a variety of ligands, including 4-methyl histamine.