Rutgers University, New Brunswick, New Jersey, USA.
Curr Opin Allergy Clin Immunol. 2012 Oct;12(5):510-6. doi: 10.1097/ACI.0b013e328357d3ba.
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.
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.
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.
通过与四个组胺受体（H1-H4）以不同亲和力结合，抗组胺药发挥药理作用，产生不同的效果取决于它们主要结合的受体。本综述的目的是通过比较它们与这些受体的结合亲和力来确定抗组胺药的相对效力。综述了抗组胺药与组胺受体结合亲和力的研究，并分析了抑制剂结合的解离常数（Ki），以确定每种受体最有效的和最不有效的抗组胺药。
我们检索了 19 种抗组胺药的结合亲和力。对于 H1 受体，哌嗪表现出最高的亲和力（Ki=0.8 nM），而噻哌酰胺的亲和力最低（Ki=280,000 nM）。对于 H2 受体，雷尼替丁表现出最高的亲和力（Ki=187 nM），而奥洛他定的亲和力最低（Ki=100,000 nM）。对于最近发现的 H3 和 H4 受体，噻哌酰胺表现出最高的亲和力（Ki=1.1 nM），奥洛他定的亲和力最低（Ki=79,400 nM）。关于结合亲和力的数据存在于 H4 受体：酮替芬、苯海拉明、雷尼替丁、西咪替丁和噻哌酰胺。在这些药物中，噻哌酰胺表现出最高的亲和力（Ki=27 nM），而西咪替丁和雷尼替丁对 H4 受体的亲和力最低（Ki>10,000 nM）。
本综述根据抗组胺药与四个组胺受体的结合亲和力总结了抗组胺药的相对效力。尽管关于抗组胺药与 H4 受体结合亲和力的数据很少，但显然，对这些组胺亚型的进一步研究可能会为治疗包括影响眼表面的过敏疾病在内的过敏疾病开辟新的途径，具有更高的治疗效果。
