Preliminary r eport
Effect of loratadine on mouse models of atopic dermatitis associated pruritus

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Abstract

To confirm the effectiveness of loratadine for relieving pruritus in atopic dermatitis, we examined the effect of this drug using animal models of atopic dermatitis associated pruritus in ICR and hairless mice. As for the results, in ICR mice, single oral administration of loratadine at a dose of 5 or 10 mg/kg significantly inhibited the dorsal scratching behavior induced by histamine or an antigen, and the effect of loratadine was more potent than that of fexofenadine and chlorpheniramine. In hairless mice, oral administration of loratadine at a dose of 10 mg/kg for 6 days significantly inhibited the facial scratching behavior induced by the feeding of a low magnesium diet. Furthermore, oral administration of loratadine at a dose of 10 mg/kg for 7 days also significantly inhibited the histamine-induced scratching behavior in the same animals. These results indicate that loratadine may be effective in preventing pruritus associated with atopic dermatitis.

Introduction

Atopic dermatitis is a condition manifesting eczema, serous papules, scaling and crust. In severe cases, erosion and infiltration were also observed [1]. It is known that atopic dermatitis generally produces severe itching of the skin, and repeated scratching further aggravates the skin symptoms [1]. Histamine has been identified as one of the substances causing itching [2]. Therefore, histamine H1-antagonists are used widely in the treatment of atopic dermatitis [1], [3]. Loratadine is a drug with selective histamine H1 blocking action, and is effective by once daily administration. It has been also reported that loratadine has superior long-acting and non-sedative properties [4]. Currently, the clinical application of loratadine is limited to allergic rhinitis and itching associated with skin diseases (eczema, dermatitis) and urticaria. It is generally recognized that H1-antagonists are effective toward pruritus associated with skin diseases, though these effects are not always sufficient. As for loratadine, however, no data are available to show whether the drug is effective in the atopic dermatitis model in animals. With the objective of confirming the effectiveness of loratadine for relieving pruritus in atopic dermatitis, the present study examined the efficacy of loratadine in various mouse models of atopic dermatitis associated pruritus.

Section snippets

Experimental animals

Female ICR mice (6–8-weeks-old; Japan SLC, Shizuoka) and female Hos:HR-1 strain hairless mice (4-weeks-old; Hoshino Laboratory Animals, Saitama, Japan) were used in this study. The animals were kept under conventional animal housing conditions at room temperature (24 ± 2 °C), a humidity of 55 ± 15%, and a 12-h light and darkness cycle. The ICR mice were fed a commercial MF diet (Oriental Yeast, Tokyo, Japan) while the hairless mice were fed a modified AIN-93G diet with low magnesium content

Effect on histamine-induced dorsal scratching behavior in ICR mice

As shown in Fig. 1, in the control group, following the intradermal injection of histamine at 100 nmol/site, the number of scratches observed during the 60 min period was 66.8 ± 18.4 (n = 10). Loratadine reduced the number of scratches in a dose-dependent manner, and a significant effect was observed at doses of 5 and 10 mg/kg. On the other hand, fexofenadine and chlorpheniramine showed no significant inhibitory effects, even at 10 and 20 mg/kg, respectively.

Effect on antigen-induced dorsal scratching behavior in ICR mice

As shown in Fig. 2, loratadine at doses

Discussion

The present study demonstrated that in ICR mice, loratadine at doses of 5 and 10 mg/kg significantly inhibited histamine-induced dorsal scratching behavior in a dose-dependent manner, and the drug also significantly inhibited the antigen-induced scratching behavior at a dose of 10 mg/kg. In contrast, fexofenadine and chlorpheniramine showed no significant inhibition on both histamine- and antigen-induced scratching behavior even at doses of 10 and 20 mg/kg, respectively. ICR mice are considered

References (16)

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