The long duration of action of the second generation antihistamine bilastine coincides with its long residence time at the histamine H1 receptor

Reggie Bosma, Jelle van den Bor, Henry F. Vischer, Luis Labeaga, Rob Leurs*

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

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 (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.

Original languageEnglish
Pages (from-to)107-111
Number of pages5
JournalEuropean Journal of Pharmacology
Volume838
Early online date7 Sep 2018
DOIs
Publication statusPublished - 5 Nov 2018

Keywords

  • Antagonism
  • Bilastine
  • Dissociation rate constant
  • Duration of action
  • Histamine H receptor
  • Residence time

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