Preclinical pharmacology of bilastine, a new selective histamine H1 receptor antagonist: receptor selectivity and in vitro antihistaminic activity.
OBJECTIVE
This study aimed to establish the receptor selectivity and antihistaminic activity of bilastine, a new selective antihistamine receptor antagonist.


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 guinea-pig 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, alpha1-adrenoceptors, beta2-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.
Corcóstegui
Reyes
R
Department of Research, FAES FARMA, SA, Leioa, Spain.
Labeaga
Luis
L
Innerárity
Ana
A
Berisa
Agustin
A
Orjales
Aurelio
A
D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001667:Binding, Competitive; D002460:Cell Line; D004353:Drug Evaluation, Preclinical; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009928:Organ Specificity; D010880:Piperidines / Q000494:pharmacology*; D011485:Protein Binding; D011817:Rabbits; D051381:Rats; D011969:Receptors, Histamine H1 / Q000378:metabolism*
D001562:Benzimidazoles; D006634:Histamine H1 Antagonists; D010880:Piperidines; D011969:Receptors, Histamine H1; C445659:bilastine