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Anti-Inflammatory Actions of Histamine H1 Receptor Antagonists Unrelated to H1 Receptor Blockade

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Histamine H1 receptor antagonists (antihistamines) are widely used for treatment of allergic conditions such as rhinitis, urticaria and atopic dermatitis. A number of first- and second-generation compounds are available; all prevent the pro-inflammatory pharmacological actions of histamine related to allergy and inflammation through competitive antagonism at H1 receptors.

In addition, both in vitro and animal studies suggest that second-generation antihistamines may also show anti-inflammatory effects unrelated to H1 receptor antagonism. These effects include inhibition of the functions of several effector and regulator cells of inflammation, such as degranulation of mast cells, oxygen radical release from eosinophils and neutrophils, lipid mediator generation from eosinophils, and eosinophil cell migration. Although their precise mode of action is incompletely understood, H1 antagonists may interfere with cellular transmembrane signalling processes, including Ca++ transmembrane flux and intracellular mobilisation, accumulation of intracellular adenosine 3′,5′-monophosphate (cyclic AMP), and the activities of both protein kinase C and NADPH oxidase. Whether or not H1 antagonists mediate these effects via binding to histamine receptor subtypes other than H1 remains, as yet, unclear.

This review discusses the clinical effects and the putative mode of anti-inflammatory action unrelated to H1 receptor blockade of this class of drugs.

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Correspondence to Professor Dr Claus Kroegel.

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Kroegel, C., Herzog, V., Knöchel, B. et al. Anti-Inflammatory Actions of Histamine H1 Receptor Antagonists Unrelated to H1 Receptor Blockade. Clin. Immunother. 5, 449–464 (1996). https://doi.org/10.1007/BF03259340

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  • Histamine
  • Platelet Activate Factor
  • Allergy Clin Immunol
  • Terfenadine
  • Cetirizine