کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10158427 1666526 2018 20 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The long duration of action of the second generation antihistamine bilastine coincides with its long residence time at the histamine H1 receptor
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
The long duration of action of the second generation antihistamine bilastine coincides with its long residence time at the histamine H1 receptor
چکیده انگلیسی
Drug-target binding kinetics has recently attracted considerable interest in view of the potential predictive power for in vivo drug efficacy. The recently introduced antihistamine bilastine has a long duration of in vivo drug action, which outlasts pharmacological active bilastine concentrations in blood. To provide a molecular basis for the long duration of action, we explored the kinetics of bilastine binding to the human histamine H1 receptor using [3H]mepyramine binding studies and compared its pharmacodynamics properties to the reference compounds fexofenadine and diphenhydramine, which have a long (60 ± 20 min) and short (0.41 ± 0.1 min) residence time, respectively. Bilastine shows a long drug-target residence time at the H1 receptor (73 ± 5 min) and this results in a prolonged H1 receptor antagonism in vitro (Ca2+ mobilization in Fluo-4 loaded HeLa cells), following a washout of unbound antagonist. Hence, the long residence time of bilastine can explain the observed long duration of drug action in vivo.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 838, 5 November 2018, Pages 107-111
نویسندگان
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