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Histamine receptor‐subtype affinities, selectivities, and potencies of emedastine, a novel H 1 ‐selective antagonist, and other ocularly employed antihistamines
Author(s) -
Sharif Najam A.,
Xu Shouxi,
Yanni John M.
Publication year - 1994
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430330408
Subject(s) - chemistry , antihistamine , pharmacology , histamine , antagonist , histamine receptor , terfenadine , receptor , histamine h1 receptor , medicine , biochemistry
Emedastine, a novel ocular antihistamine, exhibited nanomolar affinity (K i = 1.26 nM; pK i = 8.9) for the histamine H 1 ‐receptor and had a markedly lower affinity for histamine H 2 ‐(K i = 39.8 μM; pK i = 4.4) and H 3 ‐(K i = 12.6 μM; pK i = 4.9) receptor subtypes. Emedastine was the most H 1 ‐selective antagonist tested, being 31,200 and 10,080 times more active at the H 1 ‐receptor than at H 2 ‐ and H 3 ‐receptors, respectively. In contrast, while other ocularly employed antihistamines like pyrilamine, ketotifen, levocabastine, antazoline, and pheniramine had relatively high affinities for the H 1 ‐receptor, they exhibited significantly lower H 1 ‐selectivities than emedastine. In general, the H 1 ‐receptor affinities of the compounds compared well with their potencies for antagonizing histamine‐induced phosphoinositide (PI) turnover. Emedastine exhibited antagonist potencies (IC 50 values) of 1.8, 1.58, and 0.5 nM in human conjunctival epithelial cells, transformed human trabecular meshwork cells, and human corneal fibroblasts, respectively. In conclusion, emedastine is a high affinity and high potency histamine receptor antagonist with a superior H 1 ‐selectivity than other antihistamines tested. Emedastine may therefore be a useful antihistamine for treating symptoms of ocular allergic diseases. © 1994 Wiley‐Liss, Inc.