Antipruritic Effect of the Topical Phosphodiesterase 4 Inhibitor E6005 Ameliorates Skin Lesions in a Mouse Atopic Dermatitis Model

摘要: Phosphodiesterase (PDE) 4 inhibition is a well-known anti-inflammatory mechanism, but the development of PDE4 inhibitors has been hampered by side effects such as nausea and emesis. Local delivery inhibitor to site inflammation may overcome these issues. The purpose this study was assess therapeutic potential E6005 (methyl 4-[({3-[6,7-dimethoxy-2-(methylamino)quinazolin-4-yl]phenyl}amino)carbonyl]benzoate), novel developed topical agent for atopic dermatitis (AD). potently selectively inhibited human activity with an IC₅₀ 2.8 nM suppressed production various cytokines from lymphocytes monocytes values ranging 0.49 3.1 nM. In mice models, application produced immediate antipruritic effect well reduced expression cytokines/adhesion molecules. On basis observed effects, ameliorated appearance dermatitis-like skin lesions in two types AD hapten- mite-elicited exhibiting inhibitory comparable that tacrolimus. use ¹⁴C-labeled showed rapid clearance blood low distribution brain, contributing emetic compound. These results suggest be promising treatment AD.