Drugs in R & D

, Volume 6, Issue 6, pp 371–384

Preclinical Pharmacology of Bilastine, a New Selective Histamine H1 Receptor Antagonist

Receptor Selectivity and in Vitro Antihistaminic Activity
  • Reyes Corcóstegui
  • Luis Labeaga
  • Ana Innerárity
  • Agustin Berisa
  • Aurelio Orjales
Original Research Article

Abstract

Objective: This study aimed to establish the receptor selectivity and antihistaminic activity of bilastine, a new selective antihistamine receptor antagonist.

Design and methods:In vitro experiments were conducted using a receptor binding screening panel and guinea-pig and rat tissues. Antihistaminic activity was determined using H1 receptor binding studies and in vitro H1 antagonism studies conducted in guinea-pig tissues and human cell lines. Receptor selectivity was established using a receptor binding screening panel and a receptor antagonism screening conducted in guinea-pig, rat and rabbit tissues. Inhibition of inflammatory mediators was determined through the Schultz-Dale reaction in sensitised guinea-pig ileum.

Results: Bilastine binds to histamine H1-receptors as indicated by its displacement of [3H]-pyrilamine from H1-receptors expressed in guinea-pig cerebellum and human embryonic kidney (HEK) cell lines. The studies conducted on guineapig smooth muscle demonstrated the capability of bilastine to antagonise H1-receptors. Bilastine is selective for histamine H1-receptors as shown in receptor-binding screening conducted to determine the binding capacity of bilastine to 30 different receptors. The specificity of its H1-receptor antagonistic activity was also demonstrated in a series of in vitro experiments conducted on guinea-pig and rat tissues. The results of these studies confirmed the lack of significant antagonism against serotonin, bradykinin, leukotriene D4, calcium, muscarinic M3-receptors, α1-adrenoceptors, β2-adrenoceptors, and H2- and H3-receptors. The results of the in vitro Schultz-Dale reaction demonstrated that bilastine also has anti-inflammatory activity.

Conclusions: These preclinical studies provide evidence that bilastine has H1-antihistamine activity, with high specificity for H1-receptors, and poor or no affinity for other receptors. Bilastine has also been shown to have anti-inflammatory properties.

References

  1. 1.
    Slater JW, Zechnich AD, Haxby DG. Second-generation antihistamines: a comparative review. Drugs 1999; 57 (1): 31–47PubMedCrossRefGoogle Scholar
  2. 2.
    Yap YG, Camm AJ. The current cardiac safety situation with antihistamines. Clin Exp Allergy 1999; 29 Suppl. 1: 15–24PubMedGoogle Scholar
  3. 3.
    Benavides J, Schoemaker H, Dana C, et al. In vitro and in vivo interaction of the novel selective histamine H1 receptor antagonist mizolastine with H1 receptors in rodents. Arzneimittel Forschung 1995; 45 (5): 551–8PubMedGoogle Scholar
  4. 4.
    McPherson GA. A personal computer-based approach to the analysis of radioligand binding experiments. Comput Programs Biomed 1983; 17: 107–14PubMedCrossRefGoogle Scholar
  5. 5.
    Smit JM, Timmerman H, Hijzelendoorn JC, et al. Regulation of the human histamine H1 receptor stably expressed in Chinese hamster ovary cells. Br J Pharmacol 1996; 117 (6): 1071–80PubMedCrossRefGoogle Scholar
  6. 6.
    Cheng YC, Prusoff WH. Relationship between the inhibition constant (K1) and the concentration of inhibitor which cause 50 per cent inhibition (IC50) of an enzymatic reaction. Biochem Pharmacol 1973; 22 (23): 3099–108PubMedCrossRefGoogle Scholar
  7. 7.
    Arunlakshana O, Schild HO. Some quantitative uses of drug antagonists. Br J Pharmacol 1959; 14 (1): 48–58Google Scholar
  8. 8.
    Van Rossum JM. 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 Ther 1963; 143: 299–330Google Scholar
  9. 9.
    Constantine JW. The spirally cut tracheal strip preparation. J Pharmacol 1965; 17: 384–5CrossRefGoogle Scholar
  10. 10.
    Fukuda T, Saito T, Tajima S, et al. Antiallergic effect of 1-(2-ethoxyethyl)-2-(4-methyl-1-homopiperazinyl) benzimidazole difumarate (KB-2413). Arzneimittel Forschung 1984; 34 (7): 805–10PubMedGoogle Scholar
  11. 11.
    Lim HD, van Rijn RM, Ling P, et al. Evaluation of histamine H1-, H2-, and H3-receptor ligands at the human histamine H4 receptor: identification of 4-methylhistamine as the first potent and selective histamine H4 receptor agonist. J Pharmacol Exp Ther 2005 Jun 9 [Epub ahead of print]Google Scholar

Copyright information

© Adis Data Information BV 2005

Authors and Affiliations

  • Reyes Corcóstegui
    • 1
  • Luis Labeaga
    • 1
  • Ana Innerárity
    • 1
  • Agustin Berisa
    • 1
  • Aurelio Orjales
    • 1
  1. 1.Department of ResearchFAES FARMA, SALeioaSpain

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