Preclinical Pharmacology of Bilastine, a New Selective Histamine H1 Receptor AntagonistReceptor Selectivity andin VitroAntihistaminic Activity
作者:
Reyes Corcóstegui,
Luis Labeaga,
Ana Innerárity,
Agustin Berisa,
Aurelio Orjales,
期刊:
Drugs in R & D
(ADIS Available online 2005)
卷期:
Volume 6,
issue 6
页码: 371-384
ISSN:1174-5886
年代: 2005
出版商: ADIS
关键词: Antihistamines, pharmacodynamics;Bilastine, pharmacodynamics;Research and development
数据来源: ADIS
摘要:
ObjectiveThis study aimed to establish the receptor selectivity and antihistaminic activity of bilastine, a new selective antihistamine receptor antagonist.Design and methodsIn vitroexperiments were conducted using a receptor binding screening panel and guinea-pig and rat tissues. Antihistaminic activity was determined using H1receptor binding studies andin vitroH1antagonism 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.ResultsBilastine 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 ofin vitroexperiments 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 thein vitroSchultz-Dale reaction demonstrated that bilastine also has anti-inflammatory activity.ConclusionsThese 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.
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