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Ophthalmic antihistamines and H1–H4 receptors

Wade, Laurie; Bielory, Leonard; Rudner, Shara

Current Opinion in Allergy and Clinical Immunology: October 2012 - Volume 12 - Issue 5 - p 510–516
doi: 10.1097/ACI.0b013e328357d3ba
EYE ALLERGY: Edited by Leonard Bielory and Stefano Bonini

Purpose of review Antihistamines exert pharmacologic effects by binding to four histamine receptors (H1–H4) 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 H1 receptors, pyrilamine exhibited the highest affinity (Ki = 0.8 nM), and thioperamide the lowest (Ki = 280 000 nM). For H2 receptors, ranitidine exhibited the highest affinity (Ki = 187 nM), and olopatadine the lowest (Ki = 100 000 nM). For the recently discovered H3 and H4 receptors, thioperamide exhibited the highest affinity (Ki = 1.1 nM), and olopatadine exhibited the lowest (Ki = 79 400 nM), to H3. Data on binding affinities to the H4 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 H4 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 H4 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.

aRutgers University, New Brunswick, New Jersey

bRobert Wood Johnson University Hospital New Brunswick

cSTARx Allergy and Asthma Center, Springfield

dBelvidere Pharmacy, Highland Park, New Jersey, USA

Correspondence to Shara Rudner, 440 A Raritan Ave, Highland Park, NJ 08904, USA. Tel: +1 908 756 6695/202; e-mail:

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