1. The long duration of action of the second generation antihistamine bilastine coincides with its long residence time at the histamine H 1 receptor.
- Author
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Bosma R, van den Bor J, Vischer HF, Labeaga L, and Leurs R
- Subjects
- Diphenhydramine pharmacology, HeLa Cells, Humans, Terfenadine analogs & derivatives, Terfenadine pharmacology, Time Factors, Benzimidazoles pharmacology, Histamine H1 Antagonists, Non-Sedating pharmacology, Piperidines pharmacology, Receptors, Histamine H1 metabolism
- 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 H
1 receptor using [3 H]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., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)- Published
- 2018
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