Emedastine: a potent, high affinity histamine H1-receptor-selective antagonist for ocular use: receptor binding and...

The antihistaminic agent, emedastine, was tested for its ability to compete for [3H]pyrilamine, [3H]tiotidine and [3H]N-methyl histamine binding to rodent brain H1, H2 and H3 histamine receptors, respectively. 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.