Agents and Actions

, Volume 19, Issue 3–4, pp 164–168 | Cite as

Antagonism of histamine and leukotrienes by azelastine in isolated guinea pig ileum

  • N. Chand
  • W. Diamantis
  • R. D. Sofia
Histamine and Kinins


The effects of azelastine on histamine- and leukotriene C4 and D4 (LTC4, LTD4)-induced contractile responses in isolated guinea pig ileum were investigated. Following a 2-min contact with the ileum, azelastine produced competitive antagonism of histamine (pA2=8.24). Following a 15-min contact, azelastine at 2.5×10−9 M exerted competitive antagonism, but at higher concentrations (10, 40 and 160×10−9M) it not only shifted histamine concentration-effect curves to the right but also suppressed its maximum. Thus, azelastine exerts a dual (competitive/noncompetitive) antagonism of histamine depending upon the concentration and duration of contact. Azelastine and FPL 55712 (a known LT receptor antagonist) produced concentration-dependent antagonism of LTC4 and LTD4. Azelastine and compound FPL 55712 also exerted concentration-dependent reversal (relaxation) of pre-existing LTC4-induced contractions. In conclusion, the potent H1-histamine and leukotriene receptor blocking activities of azelastine may contribute to its antiasthmatic/antiallergic activities.


Receptor Antagonist Histamine Receptor Blocking Contractile Response Blocking Activity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. [1]
    J. P. Kemp, E. O. Meltzer, H. A. Orgel, M. J. Welch, R. F. Lockey, E. Middleton, Jr., S. L. Spector, J. L. Perhach and J. J. Newton,A Dose-Response Study of the Bonchodilator Action of Azelastine in Asthma. J. Allergy Clin. Immunol.77, 249 (1986).Google Scholar
  2. [2]
    S. Motojima, Y. Ohashi, T. Otsuka, T. Fukuda and S. Makino,Effects of Azelastine on Allergen- and Exercise-Induced Asthma. Asian Pacific J. Allergy Immunol.3, 174–178 (1985).Google Scholar
  3. [3]
    S. Spector, A. Rohr, G. Rachelefsy, R. Katz, S. Siegle, J. Perhach and J. Newton,Pharmacodynamic Evaluation of Azelastine in Asthmatics. J. Allergy Clin. Immunol.77, 249 (1986).Google Scholar
  4. [4]
    J. T. Connell, J. L. Perhach, J. M. Weiler, R. Rosenthale, L. Hamilton, L. Diamond and J. J. Newton,Azelastine a New Antiallergic Agent: Efficacy in Ragweed Hay Fever. Annals of Allergy55, 392 (1985).Google Scholar
  5. [5]
    C. A. Gould, S. Ollier and R. J. Davies,The Effect of Single and Multiple Dose Therapy With Azelastine on the Immediate Asthmatic Response to Allergen Provocation Testing. Annals of Allergy55, 232 (1985).Google Scholar
  6. [6]
    W. Storms, E. Middleton, D. Dvorin, J. Kemp, S. Spector, J. Newton and J. L. Perhach,Azelastine (AZEL) in the Treatment of Asthma. J. Allergy Clin. Immunol.75, 167 (1985).Google Scholar
  7. [7]
    J. Perhach, J. Connell, L. Hamilton, L. Diamond, J. Weiler and J. Melvin,Multicenter Trial of Azelastine in Allergic Rhinitis. J. Allergy Clin. Immunol.73, 144 (1984).Google Scholar
  8. [8]
    A. Mandi, Y. G. Galgoc, E. Galambos and R. Aurich,Histamine Protection and Bronchodilation With Azelastine a New Antiallergic Compound. Bull. Europ. Physiopathy. Res.17, 5P (1981).Google Scholar
  9. [9]
    P. Atkins, H. Merton, P. Karpink, I. Weliky and B. Zweiman,Azelastine Inhibition of Skin Test Reactivity in Humans. J. Allergy Clin. Immunol.75, 167 (1985).Google Scholar
  10. [10]
    W. Diamantis, N. Chand, J. E. Harrison, J. Pillar, J. L. Perhach and R. D. Sofia,Inhibition of release of SRS-A and its antagonism by azelastine (A), an H 1 antagonist-antiallergic agent. Pharmacologist24, 200 (1982).Google Scholar
  11. [11]
    N. Chand, K. Nolan, W. Diamantis, J. L. Perhach, Jr. and R. D. Sofia,Inhibition of Leukotriene (SRS-A)-Mediated Allergic Bronchospasm by Azelastine, A Novel Orally Effective Antiasthmatic Drug. J. Allergy Clin. Immunol.71, 149 (1983).Google Scholar
  12. [12]
    N. Chand, J. E. Harrison, S. M. Rooney, R. D. Sofia and W. Diamantis,Inhibition of Passive Cutaneous Anaphylaxis (PCA) by Azelastine: Dissociation of its Antiallergic Activities From Antihistaminic and Antiserotonin Properties. Int. J. Immunopharmacol.7, 833–838 (1985).PubMedGoogle Scholar
  13. [13]
    N. Chand, J. Pillar, W. Diamantis and R. D. Sofia,Inhibition of Allergic Histamine Release by Azelastine and Selected Antiallergic Drugs From Rabbit Leukocytes. Int. Archs. Allergy Appl. Immunol.77, 451–455 (1985).Google Scholar
  14. [14]
    K. Taniguchi and K. Takanara,Inhibitory Effects of Various Drugs on Phorbol Myristate Acetate and n-Formyl Methionyl Leucyl Phenylalanine Induced O 2 Production in Polymorphonuclear Leukocytes. Biochem. Pharmacol.33, 3165–3169 (1984).PubMedGoogle Scholar
  15. [15]
    J. M. Van Rossum,Cumulative Dose-Response Curves. II. Technique For the Making of Dose-Response Curves in Isolated Organs and the Evaluation of Drug Parameters. Arch. int. Pharmacodyn.143, 299–349 (1963).PubMedGoogle Scholar
  16. [16]
    J. H. Gaddum, K. A. Hameed, H. E. Hathway and F. F. Stephen,Quantitative Studies of Antagonists for 5-Hydroxytryptamine. Q. J. Expt. Physiol.40, 49–74 (1955).Google Scholar
  17. [17]
    O. Arunlakshana and H. O. Schild,Some Quantitative Uses of Drug Antagonists. Br. J. Pharmacol.14, 48–58 (1959).PubMedGoogle Scholar
  18. [18]
    C. Labrid, G. Dureng, P. Duchene-Marullaz and J. Moleyre,Dualist or Pseudo-Dualist Interactions of Mepyramine, Diphenhydramine and Eprozinol With Histamine at H 1-Receptors. Jap. J. Pharmacol.27, 491–500 (1977).PubMedGoogle Scholar
  19. [19]
    T. P. Kenakin,The Classification of Drugs and Drug Receptors in Isolated Tissues. Pharmacol. Rev.36, 165–222 (1984).PubMedGoogle Scholar
  20. [20]
    B. Samuelsson,Leukotrienes: Mediators of Immediate Hypersensitivity Reactions and Inflammation. Science220, 568–575 (1983).PubMedGoogle Scholar
  21. [21]
    N. Chand and B. M. Altura,Lipoxygenase Pathway and Hydroperoxy Acids: Possible Relevance to Aspirin-Induced Asthma and Hyperirritability of Airways in Asthmatics. Prostag. & Med.6, 249–256 (1981).Google Scholar

Copyright information

© Birkhäuser Verlag 1986

Authors and Affiliations

  • N. Chand
    • 1
  • W. Diamantis
    • 1
  • R. D. Sofia
    • 1
  1. 1.Department of Pharmacology, Wallace LaboratoriesDivision of Carter-Wallace, Inc.CranburyUSA

Personalised recommendations