ANTIINFLAMMATORY ACTIONS OF HISTAMINE H-1 RECEPTOR ANTAGONISTS UNRELATED TO H-1 RECEPTOR BLOCKADE

Histamine H-1 receptor antagonists (antihistamines) are widely used fo r treatment of allergic conditions such as rhinitis, urticaria and ato pic dermatitis. A number of first- and second-generation compounds are available; all prevent the pro-inflammatory pharmacological actions o f histamine related to allergy and inflammation through competitive an tagonism at H-1 receptors. In addition, both in vitro and animal studi es suggest that second-generation antihistamines may also show anti-in flammatory effects unrelated to H-1 receptor antagonism. These effects include inhibition of the functions of several effector and regulator cells of inflammation, such as degranulation of mast cells, oxygen ra dical release from eosinophils and neutrophils, lipid mediator generat ion from eosinophils, and eosinophil cell migration. Although their pr ecise mode of action is incompletely understood, H-1 antagonists may i nterfere with cellular transmembrane signalling processes, including C a++ transmembrane flux and intracellular mobilisation, accumulation of intracellular adenosine 3',5'-monophosphate (cyclic AMP), and the act ivities of both protein kinase C and NADPH oxidase. Whether or not H-1 antagonists mediate these effects via binding to histamine receptor s ubtypes other than H-1 remains, as yet, unclear. This review discusses the clinical effects and the putative mode of anti-inflammatory actio n unrelated to H-1 receptor blockade of this class of drugs.