Roflumilast | PDE4 inhibitor

Roflumilast (162401-32-3) is a potent and selective phosphodiesterase (PDE4) inhibitor, IC₅₀=0.7, 0.9, 0.7, 0.2 nM for PDE4A1, PDE4A4, PDE4B1 and PDE4B2 respectively.¹ Clinically useful agent for treatment of COPD.² Improves sensory gating in humans³ and improves memory in rodent models⁴. Mimics calorie restriction effects via activation of AMPK/SIRT1 and protects against diabetic nephropathy.⁵ Reduces weight gain by increasing energy expenditure and improves glucose metabolism in mice.⁶

References/Citations:

1) Hatzelmann et al. (2010), The preclinical pharmacology of roflumilast—a selective, oral phosphodiesterase 4 inhibitor in development for chronic obstructive pulmonary disease; Pulm, Pharmacol. Ther., 23 235
2) Rabe et al. (2011), Update on roflumilast, a phosphodiesterase 4 inhibitor for the treatment of chronic obstructive pulmonary disease; Br. J. Pharmacol, 163 53
3) Heckman et al. (2018), Acute administration of roflumilast enhances sensory gating in healthy young humans in a randomized trial; Psychopharmacology (Berl.), 235 301
4) Vanmierlo et al. (2016), The PDE4 inhibitor roflumilast improves memory in rodents at non-emetic doses; Behav. Brain Res., 303 26
5) Tikoo et al. (2014), Calorie restriction mimicking effects of roflumilast prevents diabetic nephropathy; Biochem. Biophy. Res. Commun., 450 1581
6) Mollmann et al. (2017), The PDE4 inhibitor roflumilast reduced weight gain by increasing energy expenditure and leads to improved glucose metabolism; Diabetes Obes. Metab., 19 496