Tamura Tadafumi, Amano Toru, Ohmori Kenji, Manabe Haruhiko
Pharmaceutical Research Center, Kyowa Hakko Kogyo Co., Ltd., Nagaizumi-cho, Sunto-gun, Shizuoka, Japan.
Eur J Pharmacol. 2005 Nov 7;524(1-3):149-54. doi: 10.1016/j.ejphar.2005.09.004. Epub 2005 Nov 2.
It is suggested that atopic dermatitis is a skin disease associated with itching as subjective symptoms, and histamine H(1) receptor antagonists are used in order to prevent the itching, and the deterioration for scratch by itching. Histamine H(1) receptor selective anti-histamine olopatadine hydrochloride (olopatadine; Allelock shows consistent efficacy and safety in the treatment of allergic disorders. We investigated the possible efficacy of olopatadine on the number of scratching induced by repeated application of oxazolone in BALB/c mice. The repeated treatment of olopatadine significantly inhibited the ear swelling and the increased number of scratching. It significantly inhibited the increased production of interleukin (IL)-4, IL-1beta and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the lesioned ear. Moreover, it significantly inhibited the increased production of nerve growth factor (NGF) and substance P. On the other hand, loratadine, bepotastine and chlorpheniramine did not inhibit the ear swelling and the increased number of scratching. These results indicate that olopatadine inhibited not only the increased production of cytokines but also NGF and substance P unlike other histamine H(1) receptor antagonists. It was suggested that olopatadine suppressed the increased number of scratching by the anti-inflammatory effects. Therefore, olopatadine appears to exert additional biological effects besides its blockade of a histamine H(1) receptor.
特应性皮炎是一种以瘙痒为主要主观症状的皮肤病,组胺H(1)受体拮抗剂可用于预防瘙痒以及因瘙痒引起的搔抓恶化。组胺H(1)受体选择性抗组胺药盐酸奥洛他定(奥洛他定;阿乐洛克)在治疗过敏性疾病方面显示出一致的疗效和安全性。我们研究了奥洛他定对BALB/c小鼠反复应用恶唑酮诱导的搔抓次数的可能疗效。奥洛他定的反复治疗显著抑制了耳部肿胀和搔抓次数的增加。它显著抑制了病变耳部白细胞介素(IL)-4、IL-1β和粒细胞-巨噬细胞集落刺激因子(GM-CSF)的产生增加。此外,它显著抑制了神经生长因子(NGF)和P物质的产生增加。另一方面,氯雷他定、贝波司汀和氯苯那敏并未抑制耳部肿胀和搔抓次数的增加。这些结果表明,与其他组胺H(1)受体拮抗剂不同,奥洛他定不仅抑制了细胞因子的产生增加,还抑制了NGF和P物质的产生增加。提示奥洛他定通过抗炎作用抑制了搔抓次数的增加。因此,奥洛他定除了阻断组胺H(1)受体外,似乎还发挥了额外的生物学作用。