title: Topical E6005, a novel phosphodiesterase 4 inhibitor, attenuates spontaneous itch-related responses in mice with chronic atopy-like dermatitis.
abstract: Atopic dermatitis is a chronic inflammatory cutaneous disease with difficult-to-treat pruritus. Although phosphodiesterase (PDE) 4 inhibitors have an anti-inflammatory effect on inflammatory skin diseases, such as atopic dermatitis, their acute antipruritic activities remain unclear. Therefore, in this study, we examined whether E6005, a novel PDE4 inhibitor, has antipruritic activity in dermatitis, using a mouse model of atopic dermatitis (NC/Nga mice). A single topical application of E6005 inhibited spontaneous hind-paw scratching, an itch-associated response and spontaneous activity of the cutaneous nerve in mice with chronic dermatitis. The cutaneous concentration of cAMP was significantly decreased in mice with chronic dermatitis, and this decrease was reversed by topical E6005 application. These results suggest that E6005 increases the cutaneous concentration of cAMP to relieve dermatitis-associated itching. Thus, E6005 may be a useful therapy for pruritic dermatitis such as atopic dermatitis.
authors.affiliation: Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Tsugunobu
authors.initials: T
authors.lastname: Andoh
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Yoshida
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kuraishi
mesh_terms: D000818:Animals; D000982:Antipruritics / Q000494:pharmacology* / Q000627:therapeutic use; D000242:Cyclic AMP / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000201:enzymology; D004195:Disease Models, Animal; D007249:Inflammation; D008297:Male; D051379:Mice; D058988:Phosphodiesterase 4 Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D010795:Phthalic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D011537:Pruritus / Q000188:drug therapy* / Q000201:enzymology; D011799:Quinazolines / Q000494:pharmacology* / Q000627:therapeutic use; D015398:Signal Transduction; D012867:Skin / Q000187:drug effects
chemical_list: D000982:Antipruritics; D058988:Phosphodiesterase 4 Inhibitors; D010795:Phthalic Acids; D011799:Quinazolines; C583128:methyl 4-(((3-(6,7-dimethoxy-2-(methylamino)quinazolin-4-yl)phenyl)amino)carbonyl)benzoate; D000242:Cyclic AMP
keywords: atopic dermatitis; cAMP; itch; mice; phosphodiesterase