More than 50 H1R antihistaminics have been described with similar anti-allergy efficacy whether from first-or second-generations. However, undesirable out-of-target effects such as somnolence and cardiotoxicities were described for some first-generation antihistamines . Most probably those effects could be due to out-of-targets caused by crossing the lipophilic bloodbrain-barrier , and/or H1R crossreactivities with other HRs. More specific second-generation H1R-antihistamines such as fexofenadine, ebastine, mizolastine or astemizole, have reduced out-of-target effects. Nevertheless, astemizole and terfenadine, for instance have to be clinically retired because of inducing heart arrhythmias (i.e, ~ 0.2 µM overdose, 137 µM being lethal), most probably due to alterations of potassium channel functions .