Pharmacological properties of NIP-530, a novel therapeutic agent for atopic dermatitis

• Published in: Japanese Journal of Pharmacology Vol. 79; no. suppl.2; p. 287
• Main Authors: Yamamoto, Akiko, Iwama, Takehisa, Fujita, Yoichiro, Suzuki, Yasuhito, Takahashi, Kanako, Tsuruzoe, Nobutomo
• Format: Journal Article
• Language: English; Japanese
• Published: The Japanese Pharmacological Society 1999
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)35162-5

Atopic dermatitis is a skin disease accompanying severe pruritus that causes extremely unpleasant itching sensation. Therefore, control of pruritus is an important issue in the treatment of atopic dermatitis. In the present study, we have examined the effects of NIP-530, a newly synthesized benzimidazole derivative, on scratching behavior and ear edema in mice, and clarified its in vitro properties. NIP-530 (3-30 mg/kg, p.o.) prevented OA-induced scratch behavior in ICR mice. Neither azelastine (AZ, 1 mg/kg, p.o.) nor prednisolone 21-acetate (Pred) suppressed these responses. NIP-530 also inhibited substance P and histamine (His)-induced scratch behavior. In mice sensitized with anti-DNP IgE antibodies, NIP-530 (3-10 mg/kg, p.o.) inhibited DNFB-induced biphasic ear edema. AZ tended to inhibit only the early phase response and Pred suppressed the both phases of edema. In in vitro study, NIP-530 had an affinity for human NK1 receptor (Ki = 1.0 μM) and bovine His H1 receptor (Ki = 0.56 μM). Furthermore, NIP-530 inhibited the production of IL-4 and IL-5 from Con A stimulated human PBMC, and it also inhibited human granulocyte derived 5-lipoxygenase. These results suggest that NIP-530 inhibits scratch and skin inflammation by multiple inhibitory mechanisms, including blockage of the NK1 and His receptor. Since scratch inhibition may be related to relief of pruritus, NIP-530 is expected to be useful for the treatment of atopic dermatitis.