Drugs in R & D

, Volume 7, Issue 4, pp 219–231 | Cite as

In Vivo Pharmacological Characterisation of Bilastine, a Potent and Selective Histamine H1 Receptor Antagonist

  • Reyes Corcóstegui
  • Luis Labeaga
  • Ana Innerárity
  • Agustín Berisa
  • Aurelio Orjales
Original Research Article

Abstract

Objective: We set out to establish the in vivo histamine H1 receptor antagonistic (antihistaminic) and antiallergic properties of bilastine.

Methods:In vivo antihistaminic activity experiments consisted of measurement of: inhibition of increase in capillary permeability and reduction in microvascular extravasation and bronchospasm in rats and guinea pigs induced by histamine and other inflammatory mediators; and protection against lethality induced by histamine and other inflammatory mediators in rats. In vivo antiallergic activity experiments consisted of measurement of passive and active cutaneous anaphylactic reactions as well as type III and type IV allergic reactions in sensitised rodents.

Results: In the in vivo antihistaminic activity experiments, bilastine was shown to have a positive effect, similar to that of cetirizine and more potent than that of fexofenadine. The results of the in vivo antiallergic activity experiments showed that the properties of bilastine in this setting are similar to those observed for cetirizine and superior to fexofenadine in the model of passive cutaneous anaphylactic reaction. When active cutaneous anaphylactic reaction experiments were conducted, bilastine showed significant activity, less potent than that observed with cetirizine but superior to that of fexofenadine. Evaluation of the type III allergic reaction showed that of the antihistamines only bilastine was able to inhibit oedema in sensitised mice, although its effect in this respect was much less potent than that observed with dexamethasone. In terms of the type IV allergic reaction, neither bilastine, cetirizine nor fexofenadine significantly modified the effect caused by oxazolone.

Conclusions: The results of our in vivo preclinical studies corroborate those obtained from previously conducted in vitro experiments of bilastine, and provide evidence that bilastine possesses antihistaminic as well as antiallergic properties, with similar potency to cetirizine and superior potency to fexofenadine.

References

  1. 1.
    Labeaga L, Corcóstegui R, Innerárity A, et al. Bilastine: a novel potent, selective, and orally effective antihistamine and antiallergic drug: I. In vitro characterization. XXVI Congreso de la Sociedad Española de Farmacología; 2004 Sep 26–29; Salamanca, SpainGoogle Scholar
  2. 2.
    Corcóstegui R, Labeaga L, Innerárity A, et al. Preclinical pharmacology of bilastine, a new selective histamine H1 receptor antagonist: receptor selectivity and in vitro antihistaminic activity. Drugs R D 2005; 6: 371–84PubMedCrossRefGoogle Scholar
  3. 3.
    Corcóstegui R, Labeaga L, Orjales A. Bilastine: a novel, potent, selective, and orally effective antihistamine and antiallergic drug: II. In vivo characterization. XXVI Congreso de la Sociedad Española de Farmacología; 2004 Sep 26–29; Salamanca, SpainGoogle Scholar
  4. 4.
    Lefebvre R, Salmon J, Leconte J, et al. Influence de l’acide ε-aminocaproique sur l’augmentation de la permeabilité vasculaire chez le rat par l’histamine. CR Soc Biol 1962; 156: 183–6Google Scholar
  5. 5.
    Udaka K, Takeuchi Y, Moval H. Simple method for quantification of enhanced vascular permeability. Proc Soc Exp Biol Med 1970; 133: 1384–7PubMedGoogle Scholar
  6. 6.
    Planquois JM, Mottin G, Artola M, et al. Effects of phosphodiesterase inhibitors and salbutamol on microvascular leakage in guinea pig trachea. Eur J Pharmacol 1998; 344: 59–66PubMedCrossRefGoogle Scholar
  7. 7.
    Van Wauwe S, Awouters F, Niemegeers CJ, et al. In vivo pharmacology of astemizole, a new type of H1-antihistaminic compound. Arch Int Pharmacodyn Ther 1981; 251: 39–51PubMedGoogle Scholar
  8. 8.
    Abou-Gharbia M, Nielsen ST, Andree TH, et al. Preclinical profile of Wy-49,052, a new H1-antagonist. Drug Dev Res 1990; 21: 63–78CrossRefGoogle Scholar
  9. 9.
    Niemegeers CJE, Awouters F, Van Nueten JM, et al. Protection of rats from compound 48/80-induced lethality: a simple test for inhibitors of mast cell-mediated shock. Arch Int Pharmacodyn 1978; 134: 167–76Google Scholar
  10. 10.
    Flancbaum L, Fitzpatrick JC, Fisher H. Effect of histamine receptor antagonists on mortality in compound 48/80-induced shock. Circ Shock 1990; 32: 133–40PubMedGoogle Scholar
  11. 11.
    Konzett H, Rössler R. Versuchsanordnung zu Untersuchungen an der Bronchialmuskulatur. Arch Exp Pathol Pharmacol 1940; 195: 71CrossRefGoogle Scholar
  12. 12.
    Mota I. The mechanism of anaphylaxis: I. Production and biological properties of ‘mast cell sensitizing’ antibody. Immunology 1964; 7: 681–99PubMedGoogle Scholar
  13. 13.
    Hyung-min K, Seong-Hoon C. Lavender oil inhibits immediate-type allergic reaction in mice and rats. J Pharm Pharmacol 1999; 51: 221–6Google Scholar
  14. 14.
    Inagaki N, Miura T, Nagai H, et al. Active cutaneous anaphylaxis (ACA) in the mouse ear. Jpn J Pharmacol 1992; 59: 201–8PubMedCrossRefGoogle Scholar
  15. 15.
    Omote M, Sakai K, Mizusuawa H. Acute effect of deflazacort and its metabolite 21-desacetyl-deflazacort on allergic reactions. Arzneimittel Forschung 1994; 2: 149–53Google Scholar
  16. 16.
    Evans DP, Hossack M, Thomson DS. Inhibition of contact sensitivity in the mouse by topical application of corticosteroids. Br J Pharmacol 1971; 43: 403–8PubMedCrossRefGoogle Scholar
  17. 17.
    Van de Hoven WE, Van der Berg TP, Hall DWR, et al. Development of an ear edema model of contact hypersensitivity to avoid false-positive results due to interactions between hapten and test agents. J Pharmacol Toxicol Methods 1977; 38: 53–7CrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2006

Authors and Affiliations

  • Reyes Corcóstegui
    • 1
  • Luis Labeaga
    • 1
  • Ana Innerárity
    • 1
  • Agustín Berisa
    • 1
  • Aurelio Orjales
    • 1
  1. 1.Department of ResearchFAES FARMA, S.A.LeioaSpain

Personalised recommendations