Yanni J M, Weimer L K, Sharif N A, Xu S X, Gamache D A, Spellman J M
Ophthalmic Products Research, Alcon Laboratories Inc, Fort Worth, Tex 76134-2099, USA.
Arch Ophthalmol. 1999 May;117(5):643-7. doi: 10.1001/archopht.117.5.643.
To evaluate the effects of topical ocular drugs with histamine H1-antagonist activity on histamine-stimulated phosphatidylinositol turnover and interleukin (IL) 6 and IL-8 secretion from human conjunctival epithelial cells.
Primary human conjunctival epithelial cell cultures were stimulated with histamine in the presence or absence of test drugs. Phosphatidylinositol turnover was quantified by ion exchange chromatography and cytokine content of supernatants by enzyme-linked immunosorbent assay.
Antazoline hydrochloride, emedastine difumarate, levocabastine hydrochloride, olopatadine hydrochloride, and pheniramine maleate attenuated histamine-stimulated phosphatidylinositol turnover and IL-6 and IL-8 secretion. Emedastine was the most potent in ligand binding, phosphatidylinositol turnover, and IL-6 secretion, with dissociation constant and 50% inhibitory concentrations of 1-3 nmol/L. Olopatadine, antazoline, and pheniramine exhibited similar H1-binding affinities (32-39 nmol/L). However, olopatadine was approximately 10-fold more potent as an inhibitor of cytokine secretion (50% inhibitory concentration, 1.7-5.5 nmol/L) than predicted from binding data, while antazoline and pheniramine were far less potent (20- to 140-fold) in functional assays. Levocabastine (dissociation constant, 52.6 nmol/L) exhibited greater functional activity (50% inhibitory concentration, 8-25 nmol/L) than either antazoline or pheniramine.
Histamine-stimulated phosphatidylinositol turnover and cytokine secretion by human conjunctival epithelial cells are attenuated by compounds with H1-antagonist activity. However, antihistaminic potency alone does not predict anti-inflammatory potential. Olopatadine, emedastine, and levocabastine were notably more potent than pheniramine and antazoline.
Selected topical ocular drugs with antihistaminic activity may offer therapeutic advantages to patients with allergic conjunctivitis by inhibiting proinflammatory cytokine secretion from human conjunctival epithelial cells.
评估具有组胺H1拮抗剂活性的局部眼用药物对组胺刺激的人结膜上皮细胞磷脂酰肌醇代谢及白细胞介素（IL）-6和IL-8分泌的影响。
在存在或不存在受试药物的情况下，用组胺刺激原代人结膜上皮细胞培养物。通过离子交换色谱法定量磷脂酰肌醇代谢，通过酶联免疫吸附测定法测定上清液中的细胞因子含量。
盐酸安他唑啉、富马酸依美斯汀、盐酸左卡巴斯汀、盐酸奥洛他定和马来酸氯苯那敏可减弱组胺刺激的磷脂酰肌醇代谢及IL-6和IL-8分泌。依美斯汀在配体结合、磷脂酰肌醇代谢及IL-6分泌方面作用最强，解离常数和50%抑制浓度为1 - 3 nmol/L。奥洛他定、安他唑啉和氯苯那敏表现出相似的H1结合亲和力（32 - 39 nmol/L）。然而，奥洛他定作为细胞因子分泌抑制剂的效力（50%抑制浓度，1.7 - 5.5 nmol/L）比结合数据预测的约强10倍，而安他唑啉和氯苯那敏在功能试验中的效力则弱得多（20至140倍）。左卡巴斯汀（解离常数，52.6 nmol/L）比安他唑啉或氯苯那敏表现出更强的功能活性（50%抑制浓度，8 - 25 nmol/L）。
具有H1拮抗剂活性的化合物可减弱组胺刺激的人结膜上皮细胞磷脂酰肌醇代谢及细胞因子分泌。然而，仅抗组胺效力并不能预测抗炎潜力。奥洛他定、依美斯汀和左卡巴斯汀明显比氯苯那敏和安他唑啉效力更强。
所选具有抗组胺活性的局部眼用药物可能通过抑制人结膜上皮细胞促炎细胞因子分泌，为过敏性结膜炎患者提供治疗优势。
