In vitro activity: Ebastine at concentrations approximating those found in plasma under certain conditions suppresses in a voltage-independent manner the I(Kr) (Kd = 0.14 μM, maximum block 74%) more effectively than the slowly delayed rectifier K+ current (I(Ks)) (Kd = 0.8 μM, maximum block 60%) in guinea pig ventricular myocytes. Ebastine also suppresses IKr in HERG-expressing X. laevis oocytes with the K d value of 0.3 μM and a maximal block of 46% at 3 μM. Ebastine produces negligible effect on rat transient K+ current at concentrations of<100 nM. Ebastine is shown to block the release of anti-IgE-induced prostaglandin D2 (PGD2) and leukotriene C4/D4 from human nasal polyp cells (IC30 values of 2.57 and 9.6 μM, respectively) and to inhibit the release of cytokines. Ebastine is a novel histamine H1 receptor antagonist that combines potency with a rapid onset (fast absorption) and long duration (slow elimination) of action, at least partially mediated via the formation of an acid metabolite (carebastine) that is even more potent as an antihistamine. Ebastine has negligible activity against acetylcholine (no atropine-like adverse effects on secretions and visual accommodation) and only poorly penetrates the blood-brain barrier (no sedative adverse effects). Ebastine is without effects on the central nervous and cardiovascular systems, even after oral administration of high doses, and does not interact pharmacologically with a wide range of other drugs covering most areas of potential coadministration. Ebastine shows clear selectivity for histamine H1 as opposed to H2 receptors, has moderate activity against other potential mediators of allergic phenomena such as leukotriene C4 and platelet-activating factor, and is clearly effective against anaphylactic reactions resulting from exposure of suitably sensitised tissues or animals to antigen.