In vitro activity: Emedastine is a novel, potent, high affinity, selective, second generation H1-receptor antagonist with pre-clinically well-documented anti-allergic effects. Emedastine has Ki value of 1.3 ±0.1 nM for H1-receptors and significantly weaker affinity for H2- (K1 of 49,067 ± 11,113 nM) and H3-receptors (Ki of 12,430 ± 1,282 nM). Emedastine displays pharmacodynamic properties comparable with cetirizine and therefore qualifies as a safe and alternative compound with H1-receptor antagonist properties. Additional larger studies may be needed to substantiate potential benefits of cetirizine over emedastine after single-dose administration.

Kinase Assay: Emedastine exhibited the highest affinity for H1-receptors (dissociation constant, Ki = 1.3 +/- 0.1 nM), and was considerably weaker at H2- (K1 = 49,067 +/- 11,113 nM) and H3-receptors (Ki = 12,430 +/- 1,282 nM). These data yielded ratios of 37744, 9562 and 4 for H2:H1, H3:H1 and H2:H3 receptor affinities, respectively, thus making emedastine a very selective H1-receptor antagonist. The H1-selectivity of emedastine was considerably superior to that of pyrilamine (H2:H1, H3:H1 and H2:H3 ratios of 11887, 12709 and 1, respectively). Similarly, the respective receptor affinity ratios for ketotifen (858, 1752, 0.5), levocabastine (420, 82, 5), pheniramine (430, 312, 1), chlorpheniramine (5700, 2216, 3) and antazoline (1163, 1110, 1) showed these antihistamines to be also markedly less H1-selective than emedastine. The potency of emedastine (IC50 = 1.44 +/- 0.3 nM) for antagonizing histamine-induced phosphoinositide turnover in human trabecular meshwork cells compared well with its binding affinity at the H1-receptor. These data indicate emedastine to be a high affinity and high potency histamine antagonist with the highest selectivity for the H1-histamine receptor.

Cell Assay: