Skip to main content
SpringerLink
Log in

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

  • Histamine and Kinins
  • Published:
Agents and Actions Aims and scope Submit manuscript

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 IC50s (μM) 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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  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. 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. 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. 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. 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. N. Chand, W. Diamantis andR.D. Sofia,Antagonism of leukotrienes, calcium and histamine by azelastine, Pharmacologist26, 252 (1984).

    Google Scholar 

  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. 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. 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. 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).

    Article  Google Scholar 

  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. 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).

    Article  Google Scholar 

  13. I. Mota,The mechanism of anaphylaxis. I. Production and biological properties of ‘mast cell sensitizing’ antibody, Immunology7, 681–699 (1964).

    Google Scholar 

  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. 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. J.C. Foreman,The pharmacological control of immediate hypersensitivity, Ann. Rev. Pharmacol. Tox.21, 63–81 (1981).

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, Wallace Laboratories, Division of Carter-Wallace, Inc., 08512, Cranbury, New Jersey, USA

    N. Chand, J. Pillar, W. Diamantis & R. D. Sofia

Authors
  1. N. Chand
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. Pillar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. W. Diamantis
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R. D. Sofia
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chand, N., Pillar, J., Diamantis, W. et al. Inhibition of IgE-mediated allergic histamine release from rat peritoneal mast cells by azelastine and selected antiallergic drugs. Agents and Actions 16, 318–322 (1985). https://doi.org/10.1007/BF01982866

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01982866

Keywords

Search

Navigation