Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10158427 | European Journal of Pharmacology | 2018 | 20 Pages |
Abstract
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 (60â¯Â±â¯20â¯min) and short (0.41â¯Â±â¯0.1â¯min) residence time, respectively. Bilastine shows a long drug-target residence time at the H1 receptor (73â¯Â±â¯5â¯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.
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Authors
Reggie Bosma, Jelle van den Bor, Henry F. Vischer, Luis Labeaga, Rob Leurs,