Agents and Actions

, Volume 16, Issue 5, pp 318–322 | Cite as

Inhibition of IgE-mediated allergic histamine release from rat peritoneal mast cells by azelastine and selected antiallergic drugs

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

Abstract

The ability of azelastine to inhibit IgE-mediated allergic histamine release from the peritoneal mast cells of actively sensitized rats was investigated and compared with selected antiallergic agents. Azelastine added simultaneously with the allergic stimuli (ovalbumin, OA, 10 μg/ml + phosphatidylserine, PS, 10 μg/ml) or preincubated with cells for 10 min prior to antigen challenge produced similar concentration-dependent inhibition of allergic histamine release. The IC50sM) following 10-min preincubation were as follows: azelastine = 4.8; astemizole = 86.3; ketotifen = 112.2; diphenhydramine = 133 and theophylline = 2040.3. At IC50 level azelastine was about 18, 23, 28 and 425 times as effective as astemizole, ketotifen (newer histamine H1-receptor antagonists), diphenhydramine (a traditional H1-receptor antagonist), and theophylline (a phosphodiesterase inhibitor), respectively. Sodium cromoglycate in a concentration range or 1–1000 μM (0 or 10-min preincubation) failed to exert any inhibitory effect. These data showed that among six drugs tested azelastine is the most potent inhibitor of allergic histamine release from rat peritoneal mast cells.

References

  1. [1]
    H.J. Zechel, N. Brock, D. Lenke andU. Achterrath-Tuckermann,Pharmacological and toxicological properties of azelastine, a novel antiallergic agent, Arzneimittel-Forsch.31, 1184–1193 (1981).Google Scholar
  2. [2]
    S. Katayama, N. Imoto, H. Shionoya, T. Morimoto andY. Katah,Antiallergic effect of azelastine hydrochloride on immediate type hypersensitivity reactions in vivo and in vitro, Arzneimittel-Forsch.31, 1196–1203 (1981).Google Scholar
  3. [3]
    W. Diamantis, N. Chand, J.E. Harrison, S.M. Rooney andR.D. Sofia,Inhibition of IgE-mediated passive cutaneous anaphylaxis (PCA) by azelastine in rat, J. Allergy & Clin. Immunol.73, 184 (1984).Google Scholar
  4. [4]
    J. Perhach, J. Connell, L. Hamilton, L. Diamond, J. Weiler andJ. Melvin,Multicenter trial of azelastine in allergic rhinitis, J. Allergy & Clin. Immunol.73, 144 (1984).Google Scholar
  5. [5]
    W. Diamantis, N. Chand, J.E. Harrison, S.M. Rooney andR.D. Sofia,Dissociation of antiallergic (anti-PCA) activity from the antihistaminic and anti-serotonin activities of azelastine, Pharmacologist26, 251 (1984).Google Scholar
  6. [6]
    N. Chand, W. Diamantis andR.D. Sofia,Antagonism of leukotrienes, calcium and histamine by azelastine, Pharmacologist26, 252 (1984).Google Scholar
  7. [7]
    W. Diamantis, N. Chand, J.E. Harrison, J. Pillar, J.L. Perhach, Jr. andR.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
  8. [8]
    N. Chand, K. Nolan, W. Diamantis, J.L. Perhach, Jr. andR.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
  9. [9]
    B. Fisher andW. Schmutzler,Inhibition by azelastine of the immunologically-induced histamine release from isolated guinea pig mast cells, Arzneimittel-Forsch.31, 1193–1195 (1981).Google Scholar
  10. [10]
    N. Chand, J. Pillar, W. Diamantis, J.L. Perhach, Jr. andSofia,Inhibition of calcium ionophore (A23187)-induced histamine release by a novel anti-allergic agent, 4-(p-chlorobenzyl)-2-(hexahydro-1-methyl-1H-azepine-4yl)-1(2H)-phthalazinone hydrochloride (azelastine; A5610), Int. J. Immunopharmacol.4, 342 (1982).CrossRefGoogle Scholar
  11. [11]
    D.A.S. Fields, J. Pillar, W. Diamantis, J.L. Perhach, Jr. andR.D. Sofia,Inhibition by azelastine of nonallergic histamine release from rat peritoneal mast cells, J. Allergy & Clin. Immunol.73, 400–403 (1984).Google Scholar
  12. [12]
    N. Chand, J. Pillar, W. Diamantis, J.L. Perhach Jr. andR.D. Sofia,Inhibition of calcium ionophore (A23187)-stimulated histamine release from rat peritoneal mast cells by azelastine: Implications for its mode of action, Eur. J. Pharmac.96, 227–233 (1983).CrossRefGoogle Scholar
  13. [13]
    I. Mota,The mechanism of anaphylaxis. I. Production and biological properties of ‘mast cell sensitizing’ antibody, Immunology7, 681–699 (1964).Google Scholar
  14. [14]
    P.A. Shore, A. Burkhalter andV.H. Cohn,A method for the fluorometric assay of histamine in tissues, J. Pharmac. exp. Ther.127, 182–196 (1959).Google Scholar
  15. [15]
    L.M. Lichtenstein andA.G. Osler,Studies on the mechanisms of hypersensitivity phenomena. IX. Histamine release from leukocytes by ragweed pollen antigen, J. exp. Med.120, 507–530 (1964).Google Scholar
  16. [16]
    J.C. Foreman,The pharmacological control of immediate hypersensitivity, Ann. Rev. Pharmacol. Tox.21, 63–81 (1981).CrossRefGoogle Scholar

Copyright information

© Birkhäuser Verlag 1985

Authors and Affiliations

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

Personalised recommendations