Miadonna A, Milazzo N, Lorini M, Marchesi E, Tedeschi A
Department of Internal Medicine, University of Milan, Ospedale Maggiore Policlinico, Italy.
Int Arch Allergy Immunol. 1994 Sep;105(1):12-7. doi: 10.1159/000236797.
Loratadine is a powerful H1 antagonist commonly employed in the treatment of allergic disorders. The present study was performed to investigate whether loratadine, in addition to anti-H1 activity, is able to modulate histamine release from human basophils. Leukocyte suspensions were prepared by dextran sedimentation of peripheral venous blood drawn from 10 normal subjects. Leukocytes were stimulated with anti-IgE (1/5,000), N-formyl-methionyl-leucyl-phenylalanine (FMLP; 10 microM) and the Ca2+ ionophore A23187 (1 microM), and histamine release in the cell supernatants was measured by an automated fluorometric method. Loratadine, at concentrations ranging from 1 to 50 microM, exerted a dose-dependent inhibitory effect on IgE-mediated and IgE-independent histamine release. The concentrations inhibiting 50% of histamine release were 30 microM (anti-IgE), 29 microM (FMLP) and 24 microM (Ca2+ ionophore A23187). The inhibitory activity of loratadine was optimal after incubation for 2 h at 37 degrees C and the effect of the drug was no longer evident when leukocytes were stimulated 2 h after cell washing. Increased extracellular Ca2+ concentrations reduced the inhibitory activity of loratadine, indicating that external Ca2+ and loratadine have antagonistic effects on basophil histamine release. These results indicate that loratadine, in addition to H1 receptor blocking activity, has the capacity to inhibit histamine release from human basophils.
氯雷他定是一种强效的H1拮抗剂，常用于治疗过敏性疾病。本研究旨在调查氯雷他定除了具有抗H1活性外，是否还能够调节人嗜碱性粒细胞释放组胺。通过对10名正常受试者外周静脉血进行葡聚糖沉降来制备白细胞悬液。用抗IgE（1/5,000）、N-甲酰甲硫氨酰亮氨酰苯丙氨酸（FMLP；10 microM）和Ca2+离子载体A23187（1 microM）刺激白细胞，并通过自动荧光法测量细胞上清液中的组胺释放量。氯雷他定浓度在1至50 microM范围内时，对IgE介导的和IgE非依赖性组胺释放均产生剂量依赖性抑制作用。抑制50%组胺释放的浓度分别为30 microM（抗IgE）、29 microM（FMLP）和24 microM（Ca2+离子载体A23187）。氯雷他定在37℃孵育2小时后抑制活性最佳，细胞洗涤后2小时刺激白细胞时，药物的作用不再明显。细胞外Ca2+浓度升高会降低氯雷他定的抑制活性，表明细胞外Ca2+与氯雷他定对嗜碱性粒细胞组胺释放具有拮抗作用。这些结果表明，氯雷他定除了具有H1受体阻断活性外，还具有抑制人嗜碱性粒细胞释放组胺的能力。
