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# Chapter 11: Histamine and Antihistaminics ## Histamine Histamine, meaning "tissue amine" (histos - tissue) is almost ubiquitously present in animal tissues and in certain plants, e.g. stinging nettle. Its pharmacology was studied in detail by Dale in the beginning of the 20th century when close...

# Chapter 11: Histamine and Antihistaminics ## Histamine Histamine, meaning "tissue amine" (histos - tissue) is almost ubiquitously present in animal tissues and in certain plants, e.g. stinging nettle. Its pharmacology was studied in detail by Dale in the beginning of the 20th century when close parallelism was noted between its actions and the manifestations of certain allergic reactions. Histamine was implicated as a mediator of hypersensitivity phenomena and tissue injury reactions. It is now known to play important physiological roles. Histamine is present mostly within storage granules of mast cells. Tissues rich in histamine are: - Skin - Gastric and intestinal mucosa - Lungs - Liver - Placenta Nonmast cell histamine occurs in: - Brain - Epidermis - Gastric mucosa - Growing regions Turnover of mast cell histamine is slow, while that of nonmast cell histamine is fast. Histamine is also present in blood, most body secretions, venoms and pathological fluids. ## Synthesis, Storage and Destruction Histamine is β imidazolylethylamine. It is synthesized locally from the amino acid histidine and degraded rapidly by oxidation and methylation (Fig. 11.1). In mast cells, histamine (positively charged) is held by an acidic protein and heparin (negatively charged) within intracellular granules. When the granules are extruded by exocytosis, Na ions in e.c.f. exchange with histamine to release it free (Fig. 11.2). Increase in intracellular cAMP (caused by β adrenergic agonists and methylxanthines) inhibits histamine release. Histamine is inactive orally because liver degrades all histamine that is absorbed from the intestines. ## Histamine Receptors Four types of histaminergic receptors have now been clearly delineated and cloned. Analogous to adrenergic α and β receptors, histaminergic receptors were classified by Asch and Schild (1966) into H₁ and H₂ : those blocked by then available antihistamines were labelled H₁. Sir James Black (1972) produced the first H₁ blocker burimamide and confirmed this classification. Till now, only these two receptors are clinically relevant. A third H₃ receptor, which serves primarily as an autoreceptor controlling histamine release from neurones in the brain was identified in 1983. Though some selective H₃ agonists and antagonists have been produced, none has found any clinical application. Features of these 3 types of histaminergic receptors are compared in Table 11.1. Molecular cloning has revealed yet another (H₄) receptor in 2001 It has considerable homology with H₁ receptor and binds many H₄ ligands. 4-Methyl histamine, earlier