Olopatadine hydrochloride suppresses the rebound phenomenon after discontinuation of treatment with a topical steroid in mice with chronic contact hypersensitivity

BACKGROUND: Olopatadine hydrochloride (olopatadine; Allelock) is one of the second-generation antihistamines that are treated for allergic disorders such as rhinitis, urticaria and eczema dermatitis. Olopatadine has recently been shown to have inhibitory effects on the chronic contact hypersensitivity induced by repeated application of oxazolone in mice. Although topical steroids have widely been prescribed for atopic dermatitis, a relapse often occurs within several days after discontinuation of their prolonged use. OBJECTIVES: We investigated the possible efficacy of olopatadine against the relapse after discontinuation of prolonged use of topical prednisolone in the Balb/c mice with oxazolone-induced chronic contact hypersensitivity. METHODS: Mice with the chronic contact hypersensitivity induced by repeated application of oxazolone were treated with olopatadine as a sequential therapeutic agent. The effects of olopatadine were quantified by measurements of ear-swelling, and levels of cytokines and histamine in the lesioned ear. Results Topical prednisolone (0.05 mg/ear/day) significantly inhibited the increases in ear swelling and production of IL-1beta, IL-4, IL-18, granulocyte-macrophage colony-stimulating factor (GM-CSF) and histamine. However, after discontinuation of the treatment with topical prednisolone, the inflammation relapsed and the IL-4 level exceeded the control one. The sequential treatment with olopatadine (10 mg/kg/day) after discontinuation of the treatment with topical prednisolone alone, or topical prednisolone with olopatadine, significantly inhibited the increases in ear swelling and levels of IL-1beta, IL-4, IL-18, GM-CSF, nerve growth factor and histamine. CONCLUSIONS: These results indicate that olopatadine is an antihistamine agent having inhibitory activities against the rebound phenomenon following the discontinuation of topical steroid therapy. Olopatadine is thus expected to be a sequential therapeutic agent after discontinuation of the chronic treatment with a topical steroid.     

奥洛他定的合成

目的：合成新型H1受体阻滞剂奥洛他定。方法：以对羟基苯乙酸和苯酞为原料，经取代、环合、维蒂希反应等9步反应合成目标产物。结果与结论：合成了目标产物，其结构经MS和^1H—NMR确定。     

Effects of second-generation histamine H1 receptor antagonists on the active avoidance response in rats

1. The aim of the present study was to establish a new schedule of active avoidance response in rats to estimate the central effects of second-generation histamine H1 receptor antagonists. 2. With the new schedule, a rat was placed into a dark room. A sliding door was opened after a delay of 5 s and, unless the animal moved into the lit room, an electric shock was delivered for 3 s. With the conventional schedule, the sliding door was opened immediately after the rat was placed into the dark room. 3. Ketotifen, at a dose of 50 mg/kg, showed no significant effect on the retrieval of active avoidance response with the conventional schedule. However, with the new schedule, the drug caused significant inhibition of retrieval of the response, even at a dose of 10 mg/kg. 4. Epinastine showed no significant effect on retrieval of the active avoidance response, even at a dose of 50 mg/kg with the new schedule. 5. Cetirizine, at a dose of 50 mg/kg, caused a significant effect, indicating that cetirizine, at this dose, markedly inhibits memory retrieval. 6. Both olopatadine and loratadine had potent effects; at doses of 20 and 50 mg/kg, respectively, these agents showed significant inhibitory effects on retrieval of the response. 7. In conclusion, we have developed a new schedule of active avoidance response that can be used to estimate the central effects of second-generation histamine H1 receptor antagonists.     

ORIGINAL ARTICLE Effect of Ketotifen Fumarate,Olopatadine, and Levocabastine on Ocular Active Anaphylaxis in the Guinea Pig and Ocular Immediate Hypersensitivity in the Albino Rat

Purpose: To study the effects of ketotifen fumarate, olopatadine, and levocabastine on ocular active anaphylaxis in guinea pigs and on ocular immediate hypersensitivity in albino rats. Methods: Clinical grading scores and Evans blue dye leakage to eyelids and to eyeballs were assessed in five treatment groups (n = 10): ketotifen fumarate 0.025%, olopatadine 0.1%, levocabastine 0.05%, negative control, and positive control. Results: At 20 minutes after challenge, edema scores for ketotifen-treated guinea pigs were statistically significantly lower than those for levocabastine or olopatadine. Active treatment significantly reduced vascular leakage in both models. Ketotifen significantly reduced vascular leakage in eyelids compared with the other drugs. In guinea pigs, vascular leakage in eyeballs was significantly reduced with ketotifen fumarate compared with olopatadine and levocabastine. Conclusions: In the guinea pig model, ketotifen was more effective than olopatadine and levocabastine at reducing conjunctival edema and vascular permeability in eyelids and eyeballs. In the rat model, ketotifen was more effective at reducing vascular permeability in eyelids than olopatadine and levocabastine.     

A review of olopatadine for the treatment of ocular allergy

Ocular allergy affects > 20% of the general population and many therapeutic preparations are available to individuals experiencing the most common forms – seasonal and perennial allergic conjunctivitis. 0.1% Olopatadine topical ophthalmic solution is currently approved for the treatment of allergic signs and symptoms in patients ≥ 3 years of age. Olopatadine is available in Europe as Opatanol^® and in > 30 other countries as Patanol^®. It inhibits mast cell degranulation and antagonises histamine receptors to manage the itching, redness, chemosis, tearing and lid swelling of the ocular allergic reaction, and its mast cell stabilising ability has been demonstrated both in vitro (using human conjunctival mast cells) and in vivo (human clinical experience). This article reviews both the laboratory and clinical information available on olopatadine, prefaced by a discussion of the current understanding of the ocular allergic reaction and followed by the future implications for this compound. Both laboratory and clinical studies have established the efficacy, safety and comfort of olopatadine in several study design models and comparisons to other antiallergy medications. The application of olopatadine, specifically in the management of lid swelling, an allergic sign recalcitrant to therapy and nasal allergic symptoms has also been established. In the future, a new formulation containing 0.2% olopatadine exhibits a duration of action up to 24 h, supporting once-daily dosing.     

Effects of olopatadine in limited scleroderma with peripheral eosinophils

Scleroderma and eosinophilia often occur together, though the pathogenesis is unclear. We investigated the effect of olopatadine hydrochloride in a series of cases of limited scleroderma (LS). Ten patients with LS and positive eosinophil counts (LSE) were enrolled (average age, 85 years; six men and four women). Serum concentrations of the anti‐Scl‐70 antibody were positive. Olopatadine hydrochloride was prescribed at 10 mg/day for 3 weeks. Serum concentrations of the anti‐Scl‐70 antibody significantly decreased, but changes in eosinophil numbers and percentages in peripheral blood were not significant. Factor analysis suggested a correlation between serum concentrations of the anti‐Scl‐70 antibody and complement C⁴. Olopatadine could be effective in reducing anti‐Scl‐70 antibodies in the elderly with LSE.     

盐酸奥洛他定片治疗过敏性鼻炎疗效和安全性的多中心临床研究

目的:观察盐酸奥洛他定片治疗过敏性鼻炎的临床疗效及安全性。方法:采用随机、双盲、双模拟、多中心、平行对照的方法,试验组和对照组各150例,分别采用盐酸奥洛他定片,bid,每次1片;或氯雷他定片,qd,每次1片,2组分别给予盐酸奥洛他定和氯雷他定模拟片,连续给药14 d。疗程结束时以症状体征总积分下降值、综合疗效改善百分率来评估其临床疗效,以不良事件及不良反应、实验室检查等来评估其安全性。结果:共有147例患者纳入疗效分析,试验组(n=73)及对照组(n=74),综合疗效有效率分别为90.41%和83.78%(P>0.05)。35例患者发生54例次不良事件(试验组17人26例次,对照组18人28例次),其中48例次不良事件与药物相关,主要表现为口干、头晕、嗜睡、乏力等,此为相关药物不良反应。而2组间不良事件及不良反应发生率差异无统计学意义(P>0.05)。无严重不良事件发生。结论:盐酸奥洛他定片可有效控制过敏性鼻炎症状,疗效显著,安全性好。     

反相高效液相色谱法测定盐酸奥洛他定片的含量

目的采用反相高效液相色谱法测定盐酸奥洛他定片的含量。方法色谱柱为Zorbax SB-C18柱（250mm×4.5mm,5μm）,流动相为0.02mol/L磷酸二氢钠溶液（含0.2%辛烷基磺酸钠,用浓磷酸调pH至3.0）-乙腈（65∶35）,流速1.5mL/min,检测波长210nm,柱温为室温,进样量10μL。结果盐酸奥洛他定质量浓度在0.05～0.35g/L范围内与峰面积呈良好的线性关系（r=0.9999）,平均回收率为99.56%,RSD=0.72%（n=6）。结论所用方法专属性好,操作简便、快速,结果准确可靠,重现性好,可作为盐酸奥洛他定片的含量测定方法。     

Olopatadine hydrochloride ophthalmic solution for the treatment of allergic conjunctivitis

Introduction: Olopatadine hydrochloride is an antihistamine and mast cell stabilizer available as oral, intranasal and ocular preparations. Most of the practical applications of olopatadine therapy focus on the treatment of allergic rhinoconjunctivitis via intranasal and ocular routes.

Areas covered: This article was created from a comprehensive literature search with information taken from meta-analyses, systematic reviews, and clinical trials of children and adults. The articles that have been selected, evaluate the use of intranasal and ocular antihistamines and their role in allergic rhinoconjunctivitis.

Expert opinion: Olopatadine is significantly more effective than placebos in relieving the symptoms of allergic rhinoconjunctivitis. It can function both as a viable alternative or addition to first line therapies such as intranasal steroids and oral antihistamines.     

应用奥洛他定滴眼液等药物联合治疗过敏性结膜炎疗效分析

目的:系统评价应用奥洛他定滴眼液联合治疗过敏性结膜炎的临床疗效和安全性.方法:计算机检索PubMed、EMbase、Cochrane Library、维普中文科技期刊数据库、中国知网、万方数据库,查找国内外应用奥洛他定滴眼液联合治疗比较单独奥洛他定治疗过敏性结膜炎患者的随机对照试验(RCT),检索时限截至2016-08.国外未查到相关文献.根据纳入与排除标准纳入可分析的数据,采用Review Manager 5.3软件进行Meta分析.结果:最终纳入28个RCT,共计3 568例患者,其中治疗组1 799例,对照组1 769例.Meta分析结果显示:应用奥洛他定滴眼液联合治疗过敏性结膜炎的临床疗效均优于奥洛他定滴眼液单独治疗,其差异均有统计学意义[OR=3.54,95％ CI(2.71 ～4.61),P＜0.001].结论:应用奥洛他定滴眼液联合治疗过敏性结膜炎患者可使症状与体征显著改善,提高治疗的有效率.受纳入研究质量和数量所限,上述结论尚需进一步开展严格设计的随机双盲对照试验加以验证.