Roflumilast N-oxide is an inhibitor of phosphodiesterase 4 (PDE4; IC50 = 2 nM) and an active metabolite of the PDE4 inhibitor roflumilast .1 It is selective for PDE4 over PDE1-3 and PDE5 (IC50s = >10,000 nM for all). It reduces TNF-α-induced ICAM-1 and eotaxin levels when used in combination with prostaglandin E2 in GM06114 human fetal lung fibroblasts (IC50s = 0.9 and 0.5 nM, respectively).2 It also reduces bFGF-induced and IL-1β augmented proliferation in the same cells. Roflumilast N-oxide (2 nM) reverses cigarette smoke extract-induced reductions in ciliary beat frequency in isolated human bronchial epithelial cells.3 Roflumilast N-oxide also increases plasma glucagon-like peptide 1 (GLP-1) levels in a glucose challenge in diabetic db/db mice when administered at a dose of 10 mg/kg, as well as prevents increases in blood glucose in db/db mice at 3 mg/kg per day.4
1.Hatzelmann, A., and Schudt, C.Anti-inflammatory and immunomodulatory potential of the novel PDE4 inhibitor roflumilast in vitroJ. Pharmacol. Exp. Ther.297(1)267-279(2001) 2.Sabatini, F., Petecchia, L., Boero, S., et al.A phosphodiesterase 4 inhibitor, roflumilast N-oxide, inhibits human lung fibroblast functions in vitroPulm. Pharmacol. Ther.23(4)283-291(2010) 3.Milara, J., Armengot, M., Ba?uls, P., et al.Roflumilast N-oxide, a PDE4 inhibitor, improves cilia motility and ciliated human bronchial epithelial cells compromised by cigarette smoke in vitroBr. J. Pharmacol.166(8)2243-2262(2012) 4.Vollert, S., Kaessner, N., Heuser, A., et al.The glucose-lowering effects of the PDE4 inhibitors roflumilast and roflumilast-N-oxide in db/db miceDiabetologia55(10)2779-2788(2012)