Preclinical Pharmacology of Bilastine, a New Selective Histamine H₁ 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.