Preclinical Pharmacology of Bilastine,a New Selective Histamine H_1 Receptor Antagonist Receptor Selectivity and in Vitro Antihistaminic Activity

摘要

Objective:This study aimed to establish the receptor selectivity and antihistamin-ic 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 H_1 receptor binding studies and in vitro H_1 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 H_1-receptors as indicated by its displacement of [~3H]-pyrilamine from H_1-receptors expressed in guinea-pig cerebellum and human embryonic kidney(HEK)cell lines.The studies conducted on guinea-pig smooth muscle demonstrated the capability of bilastine to antagonise H_1-receptors.Bilastine is selective for histamine H_1-receptors as shown in receptor-binding screening conducted to determine the binding capacity of bilastine to 30 different receptors.The specificity of its H_1-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 D_4,calcium,muscarinic M_3-receptors,alpha_1-adrenoceptors,beta_2-adrenoceptors,and H_2- and H_3-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 H_1-antihistamine activity,with high specificity for H_1-receptors,and poor or no affinity for other receptors.Bilastine has also been shown to have anti-inflammatory properties.