Ophthalmic antihistamines and H1-H4 receptors

Purpose of review Antihistamines exert pharmacologic effects by binding to four histamine receptors (H-1-H-4) at different affinities, producing variable effects depending on the receptor they predominantly bind to. This review's purpose is to determine the relative potency of antihistamines by comparing their binding affinities to these receptors. Studies on binding affinities of antihistamines to histamine receptors were reviewed and the dissociation constant for inhibitor binding (Ki) analyzed to determine the most and least potent antihistamine for each receptor. Recent findings We retrieved the binding affinities for nineteen antihistamines. For H-1 receptors, pyrilamine exhibited the highest affinity (Ki = 0.8 nM), and thioperamide the lowest (Ki = 280 000 nM). For H-2 receptors, ranitidine exhibited the highest affinity (Ki = 187 nM), and olopatadine the lowest (Ki = 100 000 nM). For the recently discovered H-3 and H-4 receptors, thioperamide exhibited the highest affinity (Ki = 1.1 nM), and olopatadine exhibited the lowest (Ki = 79 400 nM), to H-3. Data on binding affinities to the H-4 receptor exist for: ketotifen, pheniramine, ranitidine, cimetidine and thioperamide. Of these, thioperamide exhibited the highest affinity (Ki = 27 nM), whereas cimetidine and ranitidine exhibited the lowest affinity (Ki = > 10 000 nM) for H-4 receptors. Summary This review summarizes the relative potency of antihistamines based on their binding affinities to the four histamine receptors. Although data on binding affinities of antihistamines to the H-4 receptor are sparse, it is apparent that further research on these histamine subtypes may open new venues for more direct treatment with a higher therapeutic efficacy on allergic disorders including those affecting the ocular surface.