Effect of olopatadine and other histamine H1 receptor antagonists on the skin inflammation induced by repeated topical application of oxazolone in mice.
Histamine H1 receptor antagonists have long been prescribed for atopic dermatitis as an adjuvant therapy with topical therapy by local applied steroids. Olopatadine is one of the second-generation histamine H1 receptor antagonists that are treated for allergic disorders. We investigated that the effect of olopatadine on oxazolone-induced chronic contact hypersensitivity response in BALB/c mice compared with other histamine H1 receptor antagonists loratadine, cetirizine and fexofenadine. The chronic contact hypersensitivity induced by repeated application of oxazolone was treated with olopatadine and other histamine H1 receptor antagonists at the effective doses on histamine-induced paw edema in mice. The effects of these drugs in the oxazolone-induced model were quantified by measurements of ear swelling, and levels of cytokines in the lesioned ear. Olopatadine significantly inhibited the ear swelling and the increased production of IL-4, IL-1beta, IL-6, GM-CSF and NGF in the lesioned ear. On the other hand, the other histamine H1 receptor antagonists did not significantly suppress the increase in ear thickness. Moreover, they did not affect the production of cytokines in the lesioned ear. These results indicate that olopatadine appears to exert additional biological effects besides its blockade of the histamine H1 receptor.
Tamura
Tadafumi
T
Pharmaceutical Research Center, Kyowa Hakko Kogyo Co., Ltd, Shizuoka, Japan. tadafumi.tamura@kyoma.co.jp
Masaki
Shigehiro
S
Ohmori
Kenji
K
Karasawa
Akira
A
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D003990:Dibenzoxepins / Q000008:administration & dosage / Q000494:pharmacology*; D003875:Drug Eruptions / Q000097:blood / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D004423:Ear; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control*; D006632:Histamine; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D007073:Immunoglobulin E / Q000097:blood; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020932:Nerve Growth Factor / Q000378:metabolism; D000069605:Olopatadine Hydrochloride; D010081:Oxazolone / Q000008:administration & dosage; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
D016207:Cytokines; D003990:Dibenzoxepins; D006634:Histamine H1 Antagonists; D010081:Oxazolone; D000069605:Olopatadine Hydrochloride; D007073:Immunoglobulin E; D006632:Histamine; D020932:Nerve Growth Factor