title: Olopatadine hydrochloride suppresses hot flashes induced by topical treatment with tacrolimus ointment in rats.
abstract: Tacrolimus ointment is prescribed for patients with atopic dermatitis, although it is known to cause transient burning sensations and hot flashes in the applied skin. The aim of this study was to evaluate the effects of olopatadine hydrochloride (olopatadine), an antiallergic agent with a histamine H1 receptor (H1R) antagonistic activity, on the incidence of hot flashes induced by topical treatment with tacrolimus ointment in rats. Consequently, the skin temperature was increased by the topical application of tacrolimus ointment in rats, and the rise in skin temperature was inhibited by pretreatment with olopatadine in a dose-dependent manner. Inhibitory effect of olopatadine on tacrolimus-induced skin temperature elevation was significantly more potent than that of cetirizine hydrochloride, other antiallergic agent with H1R antagonistic activity, at doses in which both agents exhibit comparable H1R antagonistic activity in rats. These results suggest that H1R antagonistic activity-independent mechanism contribute to the inhibitory effect of olopatadine on tacrolimus-induced skin temperature elevation. Olopatadine also significantly inhibited increases in vascular permeability and nerve growth factor production in the skin induced by topical tacrolimus treatment. Thus, the onset of hot flashes in rats is quantitatively determined by measuring the skin temperature and olopatadine attenuates hot flashes induced by topical tacrolimus ointment in rats, suggesting that the combination application with olopatadine and tacrolimus ointment is useful for improving medication adherence with tacrolimus ointment treatment in patients with atopic dermatitis.
authors.affiliation: Immunology & Allergy Research Laboratories, Research Division, Kyowa Hakko Kirin Co., Ltd., 1188 Shimotogari, Nagaizumi-cho, Sunto-gun, Shizuoka 411-8731, Japan. Electronic address: kyosuke.satake@kyowa-kirin.co.jp.
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Satake
authors.affiliation: Nephrology Research Laboratories, Research Division, Kyowa Hakko Kirin Co., Ltd., 1188 Shimotogari, Nagaizumi-cho, Sunto-gun, Shizuoka 411-8731, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Ikeda
authors.affiliation: Immunology & Allergy Research Laboratories, Research Division, Kyowa Hakko Kirin Co., Ltd., 1188 Shimotogari, Nagaizumi-cho, Sunto-gun, Shizuoka 411-8731, Japan.
authors.forename: Tadafumi
authors.initials: T
authors.lastname: Tamura
authors.affiliation: Immunology & Allergy Research Laboratories, Research Division, Kyowa Hakko Kirin Co., Ltd., 1188 Shimotogari, Nagaizumi-cho, Sunto-gun, Shizuoka 411-8731, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Amano
authors.affiliation: Immunology & Allergy Research Laboratories, Research Division, Kyowa Hakko Kirin Co., Ltd., 1188 Shimotogari, Nagaizumi-cho, Sunto-gun, Shizuoka 411-8731, Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Kobayashi
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D019584:Hot Flashes / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D020932:Nerve Growth Factor / Q000378:metabolism; D009824:Ointments; D000069605:Olopatadine Hydrochloride / Q000008:administration & dosage*; D051381:Rats; D054772:Rats, Hairless; D016559:Tacrolimus / Q000633:toxicity*; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D009824:Ointments; D000069605:Olopatadine Hydrochloride; D020932:Nerve Growth Factor; D016559:Tacrolimus
keywords: Atopic dermatitis; Cetirizine hydrochloride (PubChem CID: 55182); Hot flashes; NGF; Olopatadine; Olopatadine hydrochloride (PubChem CID: 5282402); Tacrolimus hydrate (PubChem CID: 445643); Tacrolimus ointment; Vascular permeability