Effect of Mucosal TRPV1 Inhibition in Allergic Rhinitis
Effect of Mucosal TRPV1 Inhibition in Allergic Rhinitis
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DOI：
10.1111/j.1742-7843.2011.00803.x
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发表时间：
2012-03-01
影响因子：
3.1
通讯作者：
Hogestatt, Edward D.
中科院分区：
文献类型：
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作者：
Alenmyr, Lisa;Greiff, Lennart;Hogestatt, Edward D.
瞬时受体电位香草酸-1(TRPV1)被认为是变应性鼻炎瘙痒的介质。为了解决这种可能性，我们合成了一种TRPV1阻滞剂(SB-705498)，用于季节性变应性鼻炎患者的鼻腔给药。SB-705498的药理活性在表达TRPV1的人HEK293细胞上得到证实，使用荧光钙成像技术在接受鼻辣椒素攻击的变应性鼻炎患者中得到证实。使用双盲、安慰剂对照、随机和交叉设计，研究了SB-705498在季节性变应性鼻炎患者中的作用，该患者每天接受7天的过敏原刺激。SB-705498鼻腔灌洗2min。在每一次过敏原挑战之前。主要终点为第5-7天的鼻部症状总评分。同时监测鼻腔最大吸气流量(NPIF)和鼻腔灌洗液中嗜酸性粒细胞阳离子蛋白(ECP)含量。每日局部应用SB-705498抑制辣椒素诱导的鼻部症状对季节性变应性鼻炎变应原激发患者的总症状评分、nPIF和ECP水平没有影响。个别症状，如鼻痒或打喷嚏，也没有受到影响。这些发现可能表明TRPV1不是变应性鼻炎症状的关键介质。然而，在TRPV1被排除为变应性鼻炎的药物靶点之前，应该进行额外的研究，使用作用持续时间较长的药物配方。
Transient receptor potential vanilloid-1 (TRPV1) has been implicated as a mediator of itch in allergic rhinitis. To address this possibility, we synthesized a TRPV1 blocker (SB-705498) for nasal administration in patients with seasonal allergic rhinitis. The pharmacological activity of SB-705498 was confirmed on human TRPV1-expressing HEK293 cells, using fluorometric calcium imaging, and in patients with allergic rhinitis subjected to nasal capsaicin challenges. The effect of SB-705498 was studied in patients with seasonal allergic rhinitis subjected to daily allergen challenges for 7 days, using a double-blind, placebo-controlled, randomized and cross-over design. SB-705498 was delivered by nasal lavage 2 min. before each allergen challenge. Primary end-point was total nasal symptom score on days 5-7. Nasal peak inspiratory flow (nPIF) and eosinophil cationic protein (ECP) content in nasal lavages were also monitored. Daily topical applications of SB-705498 at a concentration that inhibited capsaicin-induced nasal symptoms had no effect on total symptom score, nPIF and ECP levels in allergen-challenged patients with seasonal allergic rhinitis. The individual symptoms, nasal itch or sneezes, were also not affected. These findings may indicate that TRPV1 is not a key mediator of the symptoms in allergic rhinitis. However, additional studies, using drug formulations with a prolonged duration of action, should be conducted before TRPV1 is ruled out as a drug target in allergic rhinitis.