The effect of antihistamines on the immediate allergic response: a comparative review

Otolaryngol Head Neck Surg. 1993 Jun;108(6):723-30. doi: 10.1177/019459989310800615.


Antihistamines are believed to reduce the sneezing and rhinorrhea associated with allergic rhinitis, primarily by competitive antagonism of histamine for H1 cellular receptors, but additional mechanisms of action may contribute to their clinical efficacy. To improve our understanding of H1 antihistamine action, we studied the effects of pretreatment with terfenadine, cetirizine, ketotifen, azatadine, diphenhydramine, and azelastine on increases in vascular permeability, mast cell activation, and sneezing induced by nasal challenge with antigen. All studied antihistamines reduced sneezing, indicating that they all effectively antagonize histamine after its release. In addition, terfenadine and topically administered azatadine blocked the release of histamine. Studies with cetirizine and azelastine revealed that these antihistamines significantly reduced sulfidopeptide leukotriene levels. Terfenadine and azelastine also reduced kinin production. These results confirm that antihistamines are effective in reducing sneezing and, in some cases, vascular permeability. The findings of these studies also illustrate that the various antihistamines have multiple and different mechanisms of action that may have implications for their clinical uses.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Capillary Permeability / drug effects*
  • Cetirizine / pharmacology
  • Cyproheptadine / analogs & derivatives
  • Cyproheptadine / pharmacology
  • Diphenhydramine / pharmacology
  • Double-Blind Method
  • Histamine H1 Antagonists / pharmacology*
  • Histamine H1 Antagonists / therapeutic use
  • Humans
  • Ketotifen / pharmacology
  • Mast Cells / drug effects*
  • Peptide Hydrolases / metabolism
  • Phthalazines / pharmacology
  • Rhinitis, Allergic, Seasonal / drug therapy*
  • Rhinitis, Allergic, Seasonal / enzymology
  • Sneezing / drug effects*
  • Terfenadine / pharmacology


  • Histamine H1 Antagonists
  • Phthalazines
  • Cyproheptadine
  • Terfenadine
  • Diphenhydramine
  • azatadine
  • Peptide Hydrolases
  • tosylarginine methyl ester hydrolase
  • Ketotifen
  • Cetirizine
  • azelastine